Sara Freeman

BIRMINGHAM, ENGLAND — Foot and ankle pain affects more women than men after age 45 years, when osteoarthritis often manifests.

A systematic review of available literature from eight studies from around the world estimated that foot and ankle pain occurs in 15%–30% of women and 10%–20% of men.

It is not clear what proportion of people who have pain have OA, said Martin J. Thomas, a research physiotherapist at the Arthritis Research UK National Primary Care Centre of Keele (England) University.

Mr. Thomas, who reported the findings at the annual meeting of the British Society of Rheumatology, added that the aim of this review was to establish the baseline prevalence of ankle pain in the community in order to have a point of comparison for future work on the prevalence of symptomatic foot and ankle OA.

“Foot pain and foot problems are very common in primary care,” said Dr. Edward Roddy, a consultant rheumatologist at the Haywood Hospital in Stoke-on-Trent, England, and part of the research team at Keele University. Compared with other regional pain sites, such as the knee and hand, the foot has been studied less and “is just generally less well understood,” Dr. Roddy observed.

The researchers therefore plan to undertake a longitudinal study to better characterize the epidemiology of foot and ankle OA in primary care and determine the likely causes of foot pain. Already, the team has discovered that foot pain is the most common reason for older adults to consult a general physician.

Dr. Roddy and associates looked at the reasons for musculoskeletal foot consultations in a primary care cohort of people older than 50 years. They identified 5,706 people who were taking part in the North Staffordshire Osteoarthritis Project (NorStOP), a 3-year, population-based cohort study in which participants from three local general practices had first completed a general health survey. Patients who reported experiencing any pain in the hands, hips, knees, or feet in the previous 12 months then completed a more specific survey about their regional pain, and their permission was sought for researchers to assess their medical records and to recontact them. For the current analysis, the team looked at only those patients who reported foot pain or foot problems in the preceding 12 months, and 4,402 (71%) people allowed their medical records to be reviewed.

Linking the NorStOP data to an electronic consultations database revealed that 350 of 3,858 (9%) people in the general population cohort studied actually consulted for foot pain or problems after completing the regional pain survey, whereas 3,508 (91%) who had completed the survey did not subsequently consult.

Looking at the reasons why 9% of people consulted while the remainder who had completed the survey and reported foot pain or problems did not, the researchers found that experiencing foot pain was the most common reason for presenting to a primary care doctor for a musculoskeletal problem (odds ratio 2.04). Frequent consultations for other health problems was another significant predictor of consulting for foot pain or problems (OR 1.65).

“We've only looked at musculoskeletal consultations, so we may have underestimated consultations,” said Dr. Roddy. However, he conceded that the definition of foot pain used was very broad and that further research is needed.

Dr. Roddy said that the next challenge was to try to work out what exactly is causing the foot pain and whether this resulted from OA, another musculoskeletal condition, or perhaps another reason entirely. The Keele researchers will be performing a study asking people who consult their primary care practitioner to not only complete a questionnaire about their foot problems, but also attend the hospital for clinical examination.

Disclosures: Arthritis Research UK provided financial support for the studies. Mr. Thomas and Dr. Roddy had no relevant financial disclosure or conflicts of interest.

BIRMINGHAM, ENGLAND — Foot and ankle pain affects more women than men after age 45 years, when osteoarthritis often manifests.

A systematic review of available literature from eight studies from around the world estimated that foot and ankle pain occurs in 15%–30% of women and 10%–20% of men.

It is not clear what proportion of people who have pain have OA, said Martin J. Thomas, a research physiotherapist at the Arthritis Research UK National Primary Care Centre of Keele (England) University.

Mr. Thomas, who reported the findings at the annual meeting of the British Society of Rheumatology, added that the aim of this review was to establish the baseline prevalence of ankle pain in the community in order to have a point of comparison for future work on the prevalence of symptomatic foot and ankle OA.

“Foot pain and foot problems are very common in primary care,” said Dr. Edward Roddy, a consultant rheumatologist at the Haywood Hospital in Stoke-on-Trent, England, and part of the research team at Keele University. Compared with other regional pain sites, such as the knee and hand, the foot has been studied less and “is just generally less well understood,” Dr. Roddy observed.

The researchers therefore plan to undertake a longitudinal study to better characterize the epidemiology of foot and ankle OA in primary care and determine the likely causes of foot pain. Already, the team has discovered that foot pain is the most common reason for older adults to consult a general physician.

Dr. Roddy and associates looked at the reasons for musculoskeletal foot consultations in a primary care cohort of people older than 50 years. They identified 5,706 people who were taking part in the North Staffordshire Osteoarthritis Project (NorStOP), a 3-year, population-based cohort study in which participants from three local general practices had first completed a general health survey. Patients who reported experiencing any pain in the hands, hips, knees, or feet in the previous 12 months then completed a more specific survey about their regional pain, and their permission was sought for researchers to assess their medical records and to recontact them. For the current analysis, the team looked at only those patients who reported foot pain or foot problems in the preceding 12 months, and 4,402 (71%) people allowed their medical records to be reviewed.

Linking the NorStOP data to an electronic consultations database revealed that 350 of 3,858 (9%) people in the general population cohort studied actually consulted for foot pain or problems after completing the regional pain survey, whereas 3,508 (91%) who had completed the survey did not subsequently consult.

Looking at the reasons why 9% of people consulted while the remainder who had completed the survey and reported foot pain or problems did not, the researchers found that experiencing foot pain was the most common reason for presenting to a primary care doctor for a musculoskeletal problem (odds ratio 2.04). Frequent consultations for other health problems was another significant predictor of consulting for foot pain or problems (OR 1.65).

“We've only looked at musculoskeletal consultations, so we may have underestimated consultations,” said Dr. Roddy. However, he conceded that the definition of foot pain used was very broad and that further research is needed.

Dr. Roddy said that the next challenge was to try to work out what exactly is causing the foot pain and whether this resulted from OA, another musculoskeletal condition, or perhaps another reason entirely. The Keele researchers will be performing a study asking people who consult their primary care practitioner to not only complete a questionnaire about their foot problems, but also attend the hospital for clinical examination.

Disclosures: Arthritis Research UK provided financial support for the studies. Mr. Thomas and Dr. Roddy had no relevant financial disclosure or conflicts of interest.

BIRMINGHAM, ENGLAND — Foot and ankle pain affects more women than men after age 45 years, when osteoarthritis often manifests.

A systematic review of available literature from eight studies from around the world estimated that foot and ankle pain occurs in 15%–30% of women and 10%–20% of men.

It is not clear what proportion of people who have pain have OA, said Martin J. Thomas, a research physiotherapist at the Arthritis Research UK National Primary Care Centre of Keele (England) University.

Mr. Thomas, who reported the findings at the annual meeting of the British Society of Rheumatology, added that the aim of this review was to establish the baseline prevalence of ankle pain in the community in order to have a point of comparison for future work on the prevalence of symptomatic foot and ankle OA.

“Foot pain and foot problems are very common in primary care,” said Dr. Edward Roddy, a consultant rheumatologist at the Haywood Hospital in Stoke-on-Trent, England, and part of the research team at Keele University. Compared with other regional pain sites, such as the knee and hand, the foot has been studied less and “is just generally less well understood,” Dr. Roddy observed.

The researchers therefore plan to undertake a longitudinal study to better characterize the epidemiology of foot and ankle OA in primary care and determine the likely causes of foot pain. Already, the team has discovered that foot pain is the most common reason for older adults to consult a general physician.

Dr. Roddy and associates looked at the reasons for musculoskeletal foot consultations in a primary care cohort of people older than 50 years. They identified 5,706 people who were taking part in the North Staffordshire Osteoarthritis Project (NorStOP), a 3-year, population-based cohort study in which participants from three local general practices had first completed a general health survey. Patients who reported experiencing any pain in the hands, hips, knees, or feet in the previous 12 months then completed a more specific survey about their regional pain, and their permission was sought for researchers to assess their medical records and to recontact them. For the current analysis, the team looked at only those patients who reported foot pain or foot problems in the preceding 12 months, and 4,402 (71%) people allowed their medical records to be reviewed.

Linking the NorStOP data to an electronic consultations database revealed that 350 of 3,858 (9%) people in the general population cohort studied actually consulted for foot pain or problems after completing the regional pain survey, whereas 3,508 (91%) who had completed the survey did not subsequently consult.

Looking at the reasons why 9% of people consulted while the remainder who had completed the survey and reported foot pain or problems did not, the researchers found that experiencing foot pain was the most common reason for presenting to a primary care doctor for a musculoskeletal problem (odds ratio 2.04). Frequent consultations for other health problems was another significant predictor of consulting for foot pain or problems (OR 1.65).

“We've only looked at musculoskeletal consultations, so we may have underestimated consultations,” said Dr. Roddy. However, he conceded that the definition of foot pain used was very broad and that further research is needed.

Dr. Roddy said that the next challenge was to try to work out what exactly is causing the foot pain and whether this resulted from OA, another musculoskeletal condition, or perhaps another reason entirely. The Keele researchers will be performing a study asking people who consult their primary care practitioner to not only complete a questionnaire about their foot problems, but also attend the hospital for clinical examination.

Disclosures: Arthritis Research UK provided financial support for the studies. Mr. Thomas and Dr. Roddy had no relevant financial disclosure or conflicts of interest.

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and her associates also found there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status.

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45-51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said. “The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects. “There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop.”

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and her associates also found there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status.

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45-51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said. “The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects. “There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop.”

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and her associates also found there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status.

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45-51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said. “The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects. “There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop.”

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

Major Finding: Newborns of breast cancer patients who received chemotherapy during pregnancy did not have significantly different outcomes than did newborns of breast cancer patients who did not have chemotherapy.

Data Source: A German Breast Cancer Group registry of 235 women who were diagnosed while pregnant.

Disclosures: No disclosures were given.

BARCELONA — Women who are diagnosed with breast cancer while pregnant can be treated with standard chemotherapy regimens after the 12th gestational week without endangering the health of the fetus, according to data from a registry established by the German Breast Group.

Fetal outcomes were not significantly different when 121 newborns of women who were treated with chemotherapy were compared with 36 newborns of women who did not receive chemotherapy in pregnancy. The findings were presented in a poster at the European Breast Cancer Conference.

“Breast cancer is among the most common cancers diagnosed during pregnancy,” said the lead author Dr. Sibylle Loibl of Johann Wolfgang Goethe University in Frankfurt-am-Main, Germany. Approximately 3% of all breast cancer cases are diagnosed during pregnancy.

“In 2003, we developed the first international guidelines on how to treat breast cancer during pregnancy (Cancer 2006;106:237–46), and we found such limited data that we felt we had to collect more information about this,” she explained.

In all, 235 women with gestational breast cancer were registered in the German database between April 2003 and October 2008.

The investigators' primary aim was to evaluate fetal outcomes 4 weeks after delivery; they also plan to evaluate outcomes in the children and their mothers at 5 years after therapy.

The median age of the women was 33 years (range, 24–46 years). The diagnosis of breast cancer was made during the first trimester in 23.8% of women. Corresponding figures for the second and third trimesters were 39.5% and 36.8%, respectively.

All told, 121 women received cytotoxic chemotherapy during pregnancy. This mostly consisted of anthracyclines in 58.6%, FEC (5-fluorouracil, epirubicin, and cyclophosphamide) in 16.5%, or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) in 14%. A median of four cycles of chemotherapy was received during pregnancy.

The majority (57.1%) of women had T2 tumors, with T3 tumors found in 25.8%, T1 in 11.5% of cases, and T4 in 4.4% of women who were diagnosed with breast cancer during pregnancy. About half had node-positive disease, and 7.9% had metastatic (M1) disease. Almost two-thirds (63.5%) of breast tumors were negative for the estrogen receptor, with 34.8% identified as being HER2 positive. Most tumors (93.4%) were described as ductal invasive/other.

About half (49.3%) of all newborns in the study were delivered by cesarean section. The median time to delivery was 36 weeks, and Dr. Loibl reported that the median overall birth weight was unaffected by whether or not the mother had received chemotherapy during pregnancy. The median overall birth weight was 2,760 g for 121 newborns who were exposed, and 2,785 g for the 36 newborns who were not exposed to cytotoxic chemotherapy while in utero. No significant differences in postpartum hemoglobin levels were found, with median hemoglobin levels of 16.1 g/dL and 17.2 g/dL, respectively.

Fetal complications occurring within the first 4 weeks after birth in both sets of newborns included signs of infection, anemia, neutropenia, and the need for continuous positive airway pressure (CPAP). Some newborns who were not exposed to intrauterine chemotherapy experienced congenital malformation and icterus, whereas those who were exposed to intrauterine chemotherapy experienced rectal atresia, hyperbilirubinemia, hypoglycemia, and permanent foramen ovale.

“I think pregnant women should and can be treated with standard treatments as recommended by the international guidelines,” Dr. Loibl said. Events that occurred in fetal outcome “were similar in both groups, but we need more information on cytotoxic agents that are more commonly used, such as the taxanes.”

These findings suggest that “there is no harm done to the child when women who are pregnant take chemotherapy,” said Ellen Verschuur-van der Voort, vice president of the Dutch Breast Cancer Association and president of the Europa Donna Forum, the Netherlands.

Ms. Verschuur-van der Voort added that the research gave “a very good and positive conclusion,” offering reassurance to women who are diagnosed with breast cancer while pregnant.

Major Finding: Newborns of breast cancer patients who received chemotherapy during pregnancy did not have significantly different outcomes than did newborns of breast cancer patients who did not have chemotherapy.

Data Source: A German Breast Cancer Group registry of 235 women who were diagnosed while pregnant.

Disclosures: No disclosures were given.

BARCELONA — Women who are diagnosed with breast cancer while pregnant can be treated with standard chemotherapy regimens after the 12th gestational week without endangering the health of the fetus, according to data from a registry established by the German Breast Group.

Fetal outcomes were not significantly different when 121 newborns of women who were treated with chemotherapy were compared with 36 newborns of women who did not receive chemotherapy in pregnancy. The findings were presented in a poster at the European Breast Cancer Conference.

“Breast cancer is among the most common cancers diagnosed during pregnancy,” said the lead author Dr. Sibylle Loibl of Johann Wolfgang Goethe University in Frankfurt-am-Main, Germany. Approximately 3% of all breast cancer cases are diagnosed during pregnancy.

“In 2003, we developed the first international guidelines on how to treat breast cancer during pregnancy (Cancer 2006;106:237–46), and we found such limited data that we felt we had to collect more information about this,” she explained.

In all, 235 women with gestational breast cancer were registered in the German database between April 2003 and October 2008.

The investigators' primary aim was to evaluate fetal outcomes 4 weeks after delivery; they also plan to evaluate outcomes in the children and their mothers at 5 years after therapy.

The median age of the women was 33 years (range, 24–46 years). The diagnosis of breast cancer was made during the first trimester in 23.8% of women. Corresponding figures for the second and third trimesters were 39.5% and 36.8%, respectively.

All told, 121 women received cytotoxic chemotherapy during pregnancy. This mostly consisted of anthracyclines in 58.6%, FEC (5-fluorouracil, epirubicin, and cyclophosphamide) in 16.5%, or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) in 14%. A median of four cycles of chemotherapy was received during pregnancy.

The majority (57.1%) of women had T2 tumors, with T3 tumors found in 25.8%, T1 in 11.5% of cases, and T4 in 4.4% of women who were diagnosed with breast cancer during pregnancy. About half had node-positive disease, and 7.9% had metastatic (M1) disease. Almost two-thirds (63.5%) of breast tumors were negative for the estrogen receptor, with 34.8% identified as being HER2 positive. Most tumors (93.4%) were described as ductal invasive/other.

About half (49.3%) of all newborns in the study were delivered by cesarean section. The median time to delivery was 36 weeks, and Dr. Loibl reported that the median overall birth weight was unaffected by whether or not the mother had received chemotherapy during pregnancy. The median overall birth weight was 2,760 g for 121 newborns who were exposed, and 2,785 g for the 36 newborns who were not exposed to cytotoxic chemotherapy while in utero. No significant differences in postpartum hemoglobin levels were found, with median hemoglobin levels of 16.1 g/dL and 17.2 g/dL, respectively.

Fetal complications occurring within the first 4 weeks after birth in both sets of newborns included signs of infection, anemia, neutropenia, and the need for continuous positive airway pressure (CPAP). Some newborns who were not exposed to intrauterine chemotherapy experienced congenital malformation and icterus, whereas those who were exposed to intrauterine chemotherapy experienced rectal atresia, hyperbilirubinemia, hypoglycemia, and permanent foramen ovale.

“I think pregnant women should and can be treated with standard treatments as recommended by the international guidelines,” Dr. Loibl said. Events that occurred in fetal outcome “were similar in both groups, but we need more information on cytotoxic agents that are more commonly used, such as the taxanes.”

These findings suggest that “there is no harm done to the child when women who are pregnant take chemotherapy,” said Ellen Verschuur-van der Voort, vice president of the Dutch Breast Cancer Association and president of the Europa Donna Forum, the Netherlands.

Ms. Verschuur-van der Voort added that the research gave “a very good and positive conclusion,” offering reassurance to women who are diagnosed with breast cancer while pregnant.

Major Finding: Newborns of breast cancer patients who received chemotherapy during pregnancy did not have significantly different outcomes than did newborns of breast cancer patients who did not have chemotherapy.

Data Source: A German Breast Cancer Group registry of 235 women who were diagnosed while pregnant.

Disclosures: No disclosures were given.

BARCELONA — Women who are diagnosed with breast cancer while pregnant can be treated with standard chemotherapy regimens after the 12th gestational week without endangering the health of the fetus, according to data from a registry established by the German Breast Group.

Fetal outcomes were not significantly different when 121 newborns of women who were treated with chemotherapy were compared with 36 newborns of women who did not receive chemotherapy in pregnancy. The findings were presented in a poster at the European Breast Cancer Conference.

“Breast cancer is among the most common cancers diagnosed during pregnancy,” said the lead author Dr. Sibylle Loibl of Johann Wolfgang Goethe University in Frankfurt-am-Main, Germany. Approximately 3% of all breast cancer cases are diagnosed during pregnancy.

“In 2003, we developed the first international guidelines on how to treat breast cancer during pregnancy (Cancer 2006;106:237–46), and we found such limited data that we felt we had to collect more information about this,” she explained.

In all, 235 women with gestational breast cancer were registered in the German database between April 2003 and October 2008.

The investigators' primary aim was to evaluate fetal outcomes 4 weeks after delivery; they also plan to evaluate outcomes in the children and their mothers at 5 years after therapy.

The median age of the women was 33 years (range, 24–46 years). The diagnosis of breast cancer was made during the first trimester in 23.8% of women. Corresponding figures for the second and third trimesters were 39.5% and 36.8%, respectively.

All told, 121 women received cytotoxic chemotherapy during pregnancy. This mostly consisted of anthracyclines in 58.6%, FEC (5-fluorouracil, epirubicin, and cyclophosphamide) in 16.5%, or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) in 14%. A median of four cycles of chemotherapy was received during pregnancy.

The majority (57.1%) of women had T2 tumors, with T3 tumors found in 25.8%, T1 in 11.5% of cases, and T4 in 4.4% of women who were diagnosed with breast cancer during pregnancy. About half had node-positive disease, and 7.9% had metastatic (M1) disease. Almost two-thirds (63.5%) of breast tumors were negative for the estrogen receptor, with 34.8% identified as being HER2 positive. Most tumors (93.4%) were described as ductal invasive/other.

About half (49.3%) of all newborns in the study were delivered by cesarean section. The median time to delivery was 36 weeks, and Dr. Loibl reported that the median overall birth weight was unaffected by whether or not the mother had received chemotherapy during pregnancy. The median overall birth weight was 2,760 g for 121 newborns who were exposed, and 2,785 g for the 36 newborns who were not exposed to cytotoxic chemotherapy while in utero. No significant differences in postpartum hemoglobin levels were found, with median hemoglobin levels of 16.1 g/dL and 17.2 g/dL, respectively.

Fetal complications occurring within the first 4 weeks after birth in both sets of newborns included signs of infection, anemia, neutropenia, and the need for continuous positive airway pressure (CPAP). Some newborns who were not exposed to intrauterine chemotherapy experienced congenital malformation and icterus, whereas those who were exposed to intrauterine chemotherapy experienced rectal atresia, hyperbilirubinemia, hypoglycemia, and permanent foramen ovale.

“I think pregnant women should and can be treated with standard treatments as recommended by the international guidelines,” Dr. Loibl said. Events that occurred in fetal outcome “were similar in both groups, but we need more information on cytotoxic agents that are more commonly used, such as the taxanes.”

These findings suggest that “there is no harm done to the child when women who are pregnant take chemotherapy,” said Ellen Verschuur-van der Voort, vice president of the Dutch Breast Cancer Association and president of the Europa Donna Forum, the Netherlands.

Ms. Verschuur-van der Voort added that the research gave “a very good and positive conclusion,” offering reassurance to women who are diagnosed with breast cancer while pregnant.

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and associates also found that there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status (as of Dec. 31, 2007, when the data were censored).

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45–51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said.

“The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, she noted, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed with breast cancer.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects.

“There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop,” Dr. Saunders said.

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and associates also found that there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status (as of Dec. 31, 2007, when the data were censored).

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45–51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said.

“The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, she noted, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed with breast cancer.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects.

“There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop,” Dr. Saunders said.

Major Finding: Risk of death rose 48% when women were diagnosed with breast cancer within the 12 months after a pregnancy.

Data Source: 2,752 breast cancer patients at one center in Australia.

Disclosures: Dr. Ives and Dr. Saunders reported no conflicts of interest. Financial support for the research was provided by Susan G. Komen for the Cure and the Australian National Breast Cancer Foundation.

BARCELONA — Women younger than 45 years are 48% more likely to die if they are diagnosed with breast cancer in the first 12 months after completing a pregnancy than are other young women who are diagnosed with breast cancer and are not pregnant.

In a study of 2,752 breast cancer patients who were seen at the University of Western Australia in Crawley, Dr. Angela Ives and associates also found that there was a small (3%), but nonsignificant rise in the risk of death in women who were diagnosed with breast cancer when still pregnant.

“A possible explanation of this is that the total time a woman is pregnant, with or without lactation, correlates with increased growth of a breast cancer, and this can lead to worse survival,” Dr. Ives, a research fellow at the university, said at the European Breast Cancer Conference.

Gestational breast cancer was defined in this study as breast cancer that was diagnosed during pregnancy or in the 12-month postpartum period. “Completing pregnancy” included live births, terminations, and miscarriages.

In addition to pregnancy status, the researchers examined the effects of a variety of factors that could affect survival in the women studied. These included age at diagnosis, histologic tumor grade, disease stage, lymph node status, and length of survival and death status (as of Dec. 31, 2007, when the data were censored).

As expected, young age, positive lymph nodes, higher disease stage, and histologic tumor grade at diagnosis were associated with poor prognosis.

“When we looked at pregnancy status, those who were pregnant when they were diagnosed [n = 55] had similar survival outcomes to all those young women who had no associated pregnancy [n = 2,570],” Dr. Ives reported. “Those that were diagnosed in the first 12 months post partum [n = 127], after they completed a pregnancy, however, were 48% more likely to die than the women who were pregnant at their diagnosis.”

Dr. Ives noted that a Norwegian registry study had recently reported similar results, although in that study the postpartum period was defined as up to 6 months after completion of pregnancy (J. Clin. Oncol. 2009;27:45–51).

“Based on this research, there are two things that we would like to see happen in research, so that we can better inform women and their treating clinicians,” Dr. Ives said.

“The first is to look at how the time that a woman is pregnant or breastfeeding impacts on their survival,” she added. This would involve looking at the effects of pregnancy on survival from the time of conception to the time of breast cancer diagnosis.

“We'd also like to look at how pregnancy affects breast cancer cells,” Dr. Ives said. In the long term, pregnancy and breastfeeding are known to be protective against being diagnosed with breast cancer, she noted, but in the short term, it seems that is not the case and that it actually might increase the chances of being diagnosed with breast cancer.

Dr. Christobel Saunders, coauthor of the study and professor of surgical oncology at the university, commented that the study's findings do not change how women should currently be advised. She explained that the subjects were already diagnosed with breast cancer, and that the study did not look at possible causal or treatment effects.

“There's an intriguing biological question now which needs to be further explored about what it is about the length of pregnancy and/or breastfeeding, or perhaps the way that the body accommodates the tumor and allows a more aggressive tumor to develop,” Dr. Saunders said.

Major Finding: Pregnant breast cancer survivors had a 42% lower risk of death, compared with survivors who did not become pregnant.

Data Source: Meta-analysis of more than 19,000 women in 14 clinical trials.

Disclosures: Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, the findings of a large meta-analysis suggest they are not putting their lives at risk.

Indeed, investigators found some evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” said first author Dr. Hatem A. Azim Jr. at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

A total of 14 trials that were published between 1970 and 2009 were included in the meta-analysis.

Together these trials involved more than 19,000 women with a history of breast cancer, of whom 1,417 were pregnant and 18,059 were not pregnant at the time of study.

Women who became pregnant after being treated for breast cancer had a 42% decreased risk of dying, compared with women who did not get pregnant (hazard ratio 0.58).

Tests for publication bias and for heterogeneity did not achieve statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of the Institut Jules Bordet in Brussels.

He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ First, there could be a “healthy mother effect,” which means that the women with breast cancer who subsequently became pregnant were more likely to be healthy and less likely to experience recurrences.

Dr. Azim noted, however, that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could also be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells.

Other hormones may also be involved, he noted, and high prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ Finally, there is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses of the data are planned, and will use individual patient data where available.

Dr. Azim and his associates plan to look at how age at diagnosis (less than 35 years versus at least 35 years), the time interval between diagnosis and pregnancy (less than 2 years versus at least 2 years), lymph node status, and type of study performed (population/hospital-based versus case-control) could affect findings.

“For the time being, the take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim commented at the meeting.

“There are many guidelines but not much guidance,” commented Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh.

“The meta-analysis is very interesting, as it does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and said further information was necessary.

Major Finding: Pregnant breast cancer survivors had a 42% lower risk of death, compared with survivors who did not become pregnant.

Data Source: Meta-analysis of more than 19,000 women in 14 clinical trials.

Disclosures: Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, the findings of a large meta-analysis suggest they are not putting their lives at risk.

Indeed, investigators found some evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” said first author Dr. Hatem A. Azim Jr. at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

A total of 14 trials that were published between 1970 and 2009 were included in the meta-analysis.

Together these trials involved more than 19,000 women with a history of breast cancer, of whom 1,417 were pregnant and 18,059 were not pregnant at the time of study.

Women who became pregnant after being treated for breast cancer had a 42% decreased risk of dying, compared with women who did not get pregnant (hazard ratio 0.58).

Tests for publication bias and for heterogeneity did not achieve statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of the Institut Jules Bordet in Brussels.

He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ First, there could be a “healthy mother effect,” which means that the women with breast cancer who subsequently became pregnant were more likely to be healthy and less likely to experience recurrences.

Dr. Azim noted, however, that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could also be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells.

Other hormones may also be involved, he noted, and high prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ Finally, there is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses of the data are planned, and will use individual patient data where available.

Dr. Azim and his associates plan to look at how age at diagnosis (less than 35 years versus at least 35 years), the time interval between diagnosis and pregnancy (less than 2 years versus at least 2 years), lymph node status, and type of study performed (population/hospital-based versus case-control) could affect findings.

“For the time being, the take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim commented at the meeting.

“There are many guidelines but not much guidance,” commented Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh.

“The meta-analysis is very interesting, as it does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and said further information was necessary.

Major Finding: Pregnant breast cancer survivors had a 42% lower risk of death, compared with survivors who did not become pregnant.

Data Source: Meta-analysis of more than 19,000 women in 14 clinical trials.

Disclosures: Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, the findings of a large meta-analysis suggest they are not putting their lives at risk.

Indeed, investigators found some evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” said first author Dr. Hatem A. Azim Jr. at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

A total of 14 trials that were published between 1970 and 2009 were included in the meta-analysis.

Together these trials involved more than 19,000 women with a history of breast cancer, of whom 1,417 were pregnant and 18,059 were not pregnant at the time of study.

Women who became pregnant after being treated for breast cancer had a 42% decreased risk of dying, compared with women who did not get pregnant (hazard ratio 0.58).

Tests for publication bias and for heterogeneity did not achieve statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of the Institut Jules Bordet in Brussels.

He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ First, there could be a “healthy mother effect,” which means that the women with breast cancer who subsequently became pregnant were more likely to be healthy and less likely to experience recurrences.

Dr. Azim noted, however, that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could also be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells.

Other hormones may also be involved, he noted, and high prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ Finally, there is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses of the data are planned, and will use individual patient data where available.

Dr. Azim and his associates plan to look at how age at diagnosis (less than 35 years versus at least 35 years), the time interval between diagnosis and pregnancy (less than 2 years versus at least 2 years), lymph node status, and type of study performed (population/hospital-based versus case-control) could affect findings.

“For the time being, the take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim commented at the meeting.

“There are many guidelines but not much guidance,” commented Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh.

“The meta-analysis is very interesting, as it does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and said further information was necessary.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, they are not putting their lives at risk, according to a large meta-analysis. Indeed, investigators found evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” Dr. Hatem A. Azim Jr. said at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

The meta-analysis included 14 trials, published between 1970 and 2009, that involved more than 19,000 women with a history of breast cancer; 1,417 were pregnant and 18,059 were not pregnant at the time of study. Women who became pregnant after breast cancer treatment had a 42% decreased risk of dying compared with those who did not get pregnant. Tests for publication bias and heterogeneity did not reach statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of Institut Jules Bordet in Brussels. He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ Women with breast cancer who later became pregnant were more likely to be healthy and less likely to experience recurrences. Dr. Azim noted that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells. High prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ There is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses are planned. “The take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim said.

“There are many guidelines but not much guidance,” said Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh. “The meta-analysis … does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and that further information was necessary.

Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, they are not putting their lives at risk, according to a large meta-analysis. Indeed, investigators found evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” Dr. Hatem A. Azim Jr. said at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

The meta-analysis included 14 trials, published between 1970 and 2009, that involved more than 19,000 women with a history of breast cancer; 1,417 were pregnant and 18,059 were not pregnant at the time of study. Women who became pregnant after breast cancer treatment had a 42% decreased risk of dying compared with those who did not get pregnant. Tests for publication bias and heterogeneity did not reach statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of Institut Jules Bordet in Brussels. He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ Women with breast cancer who later became pregnant were more likely to be healthy and less likely to experience recurrences. Dr. Azim noted that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells. High prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ There is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses are planned. “The take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim said.

“There are many guidelines but not much guidance,” said Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh. “The meta-analysis … does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and that further information was necessary.

Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

BARCELONA — If women who have been successfully treated for breast cancer become pregnant, they are not putting their lives at risk, according to a large meta-analysis. Indeed, investigators found evidence that pregnancy in breast cancer survivors may confer a protective effect on overall survival.

“There is a wide perception in the oncology community that women with a history of breast cancer should not get pregnant,” Dr. Hatem A. Azim Jr. said at the European Breast Cancer Conference. “This meta-analysis strongly argues against this notion.”

The meta-analysis included 14 trials, published between 1970 and 2009, that involved more than 19,000 women with a history of breast cancer; 1,417 were pregnant and 18,059 were not pregnant at the time of study. Women who became pregnant after breast cancer treatment had a 42% decreased risk of dying compared with those who did not get pregnant. Tests for publication bias and heterogeneity did not reach statistical significance.

“Our findings clearly show that pregnancy is safe in women with a history of successfully treated breast cancer,” said Dr. Azim of Institut Jules Bordet in Brussels. He described three hypotheses as to why pregnancy might have a protective effect in breast cancer survivors:

▸ Women with breast cancer who later became pregnant were more likely to be healthy and less likely to experience recurrences. Dr. Azim noted that data from at least three studies controlled for women who relapsed at the time of pregnancy, and a protective effect of pregnancy was still observed.

▸ Hormonal effects could be involved, with some evidence that beyond a certain threshold, estrogen has an inhibitory effect on hormone receptor–positive tumor cells. High prolactin levels have been linked to a lower risk of breast cancer recurrence.

▸ There is the concept of alloimmunization, with the possibility that fetal antigens shared by tumor cells stimulate an immune response in the mother.

Further analyses are planned. “The take-home message is that women who want to get pregnant following breast cancer can do so—it's safe,” Dr. Azim said.

“There are many guidelines but not much guidance,” said Dr. Mike Dixon, clinical director of the Breakthrough Breast Cancer Research Unit in Edinburgh. “The meta-analysis … does show better survival in women who become pregnant,” he said, but he expressed concern that there was a selection bias in the trials and that further information was necessary.

Dr. Azim and Dr. Dixon reported no relevant conflicts of interest.

ROME — A 1.7% reduction in hemoglobin A_1c was achieved in patients with type 2 diabetes given the combination of sitagliptin plus metformin in a 1-year extension of a 54-week phase III trial.

This reduction, seen after 104 weeks of total follow-up, was significantly better than the reductions achieved with either drug alone or placebo, and was associated with no more adverse events than metformin monotherapy.

Dr. Debora Williams-Herman of Merck Research Laboratories in Rahway, N.J., presented the data at the annual meeting of the European Association for the Study of Diabetes.

The extension trial involved 454 patients who had already completed 1 year of treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin alone at a dose of 100 mg/day; twice-daily treatment with metformin alone at a dose of 500 mg or 1,000 mg; both drugs in combination (50 mg sitagliptin plus either 500 or 1,000 mg of metformin); or placebo and 100 mg metformin. The results of this investigation were published last year and showed that, at 54 weeks' follow-up, the mean change from baseline in hemoglobin A_1c (HbA_1c) level was −1.8% in patients given the 50-mg sitagliptin/1,000 mg metformin combination (Diabetes Care 2007;30:1979-87).

Now, at 2 years, the results show a similar and sustained reduction in HbA_1c,, compared with the original baseline values, with a −1.7% mean change in HbA_1c in the 105 patients who were treated with the sitagliptin and higher-dose metformin combination. A mean change of −1.4% in HbA_1c was reported in the 96 patients who were given the sitagliptin plus lower-dose metformin combination, with mean changes in HbA_1c of −1.3%, −1.1%, and −1.1% in the metformin 1,000 mg/day, metformin 500 mg/day, and sitagliptin 100 mg/day groups, respectively.

Almost two-thirds (60%) of patients given the sitagliptin plus higher-dose metformin combination achieved an HbA_1c below 7%, compared with 45% each for patients given the sitagliptin plus lower-dose metformin combination and those given 1,000 mg metformin. Approximately one-third (32%) of patients given sitagliptin monotherapy and 28% of those treated with metformin 500 mg achieved an HbA_1c of less than 7%.

As expected, patients who had a higher initial baseline HbA_1c achieved greater overall reductions in blood glucose over the course of the 2-year follow-up.

Dr. Williams-Herman reported that 5 of 107 patients (5%) given the sitagliptin plus higher-dose metformin combination experienced hypoglycemia during the extension study (i.e., between weeks 54 and 104). This can be compared with 2 of 100 patients (2%) given sitagliptin plus metformin 500 mg, 2 of 88 patients (2%) given metformin 1,000 mg, 1 of 85 patients (2%) given metformin 500 mg, and 1 of 42 patients (2%) given placebo and then 1,000 mg metformin. No patients given sitagliptin monotherapy developed hypoglycemia during the extension study.

“In patients with type 2 diabetes inadequately treated with diet and exercise, initial combination therapy with sitagliptin and metformin over 2 years showed substantial glycemic improvement,” she said.

Commenting on these data at a press briefing organized by Merck Sharp & Dohme, which markets sitagliptin, Dr. Bernard Charbonnel of the University Hospital of Nantes, France, said sitagliptin and metformin used together produced “powerful glycemic improvements.” He added: “Around 60% of patients achieved the HbA_1c goal of less than 7% at 2 years, which is rather impressive.”

ROME — A 1.7% reduction in hemoglobin A_1c was achieved in patients with type 2 diabetes given the combination of sitagliptin plus metformin in a 1-year extension of a 54-week phase III trial.

This reduction, seen after 104 weeks of total follow-up, was significantly better than the reductions achieved with either drug alone or placebo, and was associated with no more adverse events than metformin monotherapy.

Dr. Debora Williams-Herman of Merck Research Laboratories in Rahway, N.J., presented the data at the annual meeting of the European Association for the Study of Diabetes.

The extension trial involved 454 patients who had already completed 1 year of treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin alone at a dose of 100 mg/day; twice-daily treatment with metformin alone at a dose of 500 mg or 1,000 mg; both drugs in combination (50 mg sitagliptin plus either 500 or 1,000 mg of metformin); or placebo and 100 mg metformin. The results of this investigation were published last year and showed that, at 54 weeks' follow-up, the mean change from baseline in hemoglobin A_1c (HbA_1c) level was −1.8% in patients given the 50-mg sitagliptin/1,000 mg metformin combination (Diabetes Care 2007;30:1979-87).

Now, at 2 years, the results show a similar and sustained reduction in HbA_1c,, compared with the original baseline values, with a −1.7% mean change in HbA_1c in the 105 patients who were treated with the sitagliptin and higher-dose metformin combination. A mean change of −1.4% in HbA_1c was reported in the 96 patients who were given the sitagliptin plus lower-dose metformin combination, with mean changes in HbA_1c of −1.3%, −1.1%, and −1.1% in the metformin 1,000 mg/day, metformin 500 mg/day, and sitagliptin 100 mg/day groups, respectively.

Almost two-thirds (60%) of patients given the sitagliptin plus higher-dose metformin combination achieved an HbA_1c below 7%, compared with 45% each for patients given the sitagliptin plus lower-dose metformin combination and those given 1,000 mg metformin. Approximately one-third (32%) of patients given sitagliptin monotherapy and 28% of those treated with metformin 500 mg achieved an HbA_1c of less than 7%.

As expected, patients who had a higher initial baseline HbA_1c achieved greater overall reductions in blood glucose over the course of the 2-year follow-up.

Dr. Williams-Herman reported that 5 of 107 patients (5%) given the sitagliptin plus higher-dose metformin combination experienced hypoglycemia during the extension study (i.e., between weeks 54 and 104). This can be compared with 2 of 100 patients (2%) given sitagliptin plus metformin 500 mg, 2 of 88 patients (2%) given metformin 1,000 mg, 1 of 85 patients (2%) given metformin 500 mg, and 1 of 42 patients (2%) given placebo and then 1,000 mg metformin. No patients given sitagliptin monotherapy developed hypoglycemia during the extension study.

“In patients with type 2 diabetes inadequately treated with diet and exercise, initial combination therapy with sitagliptin and metformin over 2 years showed substantial glycemic improvement,” she said.

Commenting on these data at a press briefing organized by Merck Sharp & Dohme, which markets sitagliptin, Dr. Bernard Charbonnel of the University Hospital of Nantes, France, said sitagliptin and metformin used together produced “powerful glycemic improvements.” He added: “Around 60% of patients achieved the HbA_1c goal of less than 7% at 2 years, which is rather impressive.”

ROME — A 1.7% reduction in hemoglobin A_1c was achieved in patients with type 2 diabetes given the combination of sitagliptin plus metformin in a 1-year extension of a 54-week phase III trial.

This reduction, seen after 104 weeks of total follow-up, was significantly better than the reductions achieved with either drug alone or placebo, and was associated with no more adverse events than metformin monotherapy.

Dr. Debora Williams-Herman of Merck Research Laboratories in Rahway, N.J., presented the data at the annual meeting of the European Association for the Study of Diabetes.

The extension trial involved 454 patients who had already completed 1 year of treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin alone at a dose of 100 mg/day; twice-daily treatment with metformin alone at a dose of 500 mg or 1,000 mg; both drugs in combination (50 mg sitagliptin plus either 500 or 1,000 mg of metformin); or placebo and 100 mg metformin. The results of this investigation were published last year and showed that, at 54 weeks' follow-up, the mean change from baseline in hemoglobin A_1c (HbA_1c) level was −1.8% in patients given the 50-mg sitagliptin/1,000 mg metformin combination (Diabetes Care 2007;30:1979-87).

Now, at 2 years, the results show a similar and sustained reduction in HbA_1c,, compared with the original baseline values, with a −1.7% mean change in HbA_1c in the 105 patients who were treated with the sitagliptin and higher-dose metformin combination. A mean change of −1.4% in HbA_1c was reported in the 96 patients who were given the sitagliptin plus lower-dose metformin combination, with mean changes in HbA_1c of −1.3%, −1.1%, and −1.1% in the metformin 1,000 mg/day, metformin 500 mg/day, and sitagliptin 100 mg/day groups, respectively.

Almost two-thirds (60%) of patients given the sitagliptin plus higher-dose metformin combination achieved an HbA_1c below 7%, compared with 45% each for patients given the sitagliptin plus lower-dose metformin combination and those given 1,000 mg metformin. Approximately one-third (32%) of patients given sitagliptin monotherapy and 28% of those treated with metformin 500 mg achieved an HbA_1c of less than 7%.

As expected, patients who had a higher initial baseline HbA_1c achieved greater overall reductions in blood glucose over the course of the 2-year follow-up.

Dr. Williams-Herman reported that 5 of 107 patients (5%) given the sitagliptin plus higher-dose metformin combination experienced hypoglycemia during the extension study (i.e., between weeks 54 and 104). This can be compared with 2 of 100 patients (2%) given sitagliptin plus metformin 500 mg, 2 of 88 patients (2%) given metformin 1,000 mg, 1 of 85 patients (2%) given metformin 500 mg, and 1 of 42 patients (2%) given placebo and then 1,000 mg metformin. No patients given sitagliptin monotherapy developed hypoglycemia during the extension study.

“In patients with type 2 diabetes inadequately treated with diet and exercise, initial combination therapy with sitagliptin and metformin over 2 years showed substantial glycemic improvement,” she said.

Commenting on these data at a press briefing organized by Merck Sharp & Dohme, which markets sitagliptin, Dr. Bernard Charbonnel of the University Hospital of Nantes, France, said sitagliptin and metformin used together produced “powerful glycemic improvements.” He added: “Around 60% of patients achieved the HbA_1c goal of less than 7% at 2 years, which is rather impressive.”

ROME — Continuous glucose monitoring during pregnancy was linked to a significant reduction in median birth weight and macrosomia risk in a study of 71 women with type 1 or type 2 diabetes.

The randomized, open study also showed that pregnant women who wore the monitors for 5–7 days, at 4–6 weekly intervals, had better blood glucose control than did women who received standard prenatal care alone.

The study comprised 46 women with type 1 and 25 women with type 2 diabetes. A total of 38 women were randomized to use continuous glucose monitoring (CGM) as an educational tool to inform decision making and future therapeutic changes; the remaining 33 women were randomized to standard care, study investigator Dr. Helen R. Murphy reported Sept. 8 at the annual meeting of the European Association for the Study of Diabetes.

All statistical analyses were performed on an intention-to-treat basis, said Dr. Murphy of Ipswich (England) Hospital.

At weeks 32–36 of gestation, hemoglobin A_1c levels were significantly lower in the CGM group than in the standard care group (5.8% vs. 6.4%).

In addition, infants born to women in the CGM group were significantly less likely to have a high birth weight than were those born to women in the standard care group. The mean standard deviation (SD) score for birth weight was 0.9 for infants in the CGM group and 1.6 for those in the standard care group.

“What is even more striking is the complete absence of small-for-gestational age babies in women randomized to standard antenatal care,” Dr. Murphy said.

She also noted that there were two infants that had SD scores of above three in the CGM arm, but their mothers had withdrawn from the study before completion.

Compared with children in the standard care arm, the children in the CGM group were at decreased risk (odds ratio 0.36) of macrosomia, defined as a birth weight in the 90th percentile or higher.

CGM was well accepted by the women, according to Dr. Murphy, adding that they wore the monitors on their flank at least once a trimester. The monitors were provided free of charge by Medtronic UK. Ipswich Hospital Diabetes Centre Charity Research Fund and Diabetes UK supported the investigator-led study.

Children in the continuous glucose monitoring group had a 64% lower risk of macrosomia. DR. MURPHY

ROME — Continuous glucose monitoring during pregnancy was linked to a significant reduction in median birth weight and macrosomia risk in a study of 71 women with type 1 or type 2 diabetes.

The randomized, open study also showed that pregnant women who wore the monitors for 5–7 days, at 4–6 weekly intervals, had better blood glucose control than did women who received standard prenatal care alone.

The study comprised 46 women with type 1 and 25 women with type 2 diabetes. A total of 38 women were randomized to use continuous glucose monitoring (CGM) as an educational tool to inform decision making and future therapeutic changes; the remaining 33 women were randomized to standard care, study investigator Dr. Helen R. Murphy reported Sept. 8 at the annual meeting of the European Association for the Study of Diabetes.

All statistical analyses were performed on an intention-to-treat basis, said Dr. Murphy of Ipswich (England) Hospital.

At weeks 32–36 of gestation, hemoglobin A_1c levels were significantly lower in the CGM group than in the standard care group (5.8% vs. 6.4%).

In addition, infants born to women in the CGM group were significantly less likely to have a high birth weight than were those born to women in the standard care group. The mean standard deviation (SD) score for birth weight was 0.9 for infants in the CGM group and 1.6 for those in the standard care group.

“What is even more striking is the complete absence of small-for-gestational age babies in women randomized to standard antenatal care,” Dr. Murphy said.

She also noted that there were two infants that had SD scores of above three in the CGM arm, but their mothers had withdrawn from the study before completion.

Compared with children in the standard care arm, the children in the CGM group were at decreased risk (odds ratio 0.36) of macrosomia, defined as a birth weight in the 90th percentile or higher.

CGM was well accepted by the women, according to Dr. Murphy, adding that they wore the monitors on their flank at least once a trimester. The monitors were provided free of charge by Medtronic UK. Ipswich Hospital Diabetes Centre Charity Research Fund and Diabetes UK supported the investigator-led study.

Children in the continuous glucose monitoring group had a 64% lower risk of macrosomia. DR. MURPHY

ROME — Continuous glucose monitoring during pregnancy was linked to a significant reduction in median birth weight and macrosomia risk in a study of 71 women with type 1 or type 2 diabetes.

The randomized, open study also showed that pregnant women who wore the monitors for 5–7 days, at 4–6 weekly intervals, had better blood glucose control than did women who received standard prenatal care alone.

The study comprised 46 women with type 1 and 25 women with type 2 diabetes. A total of 38 women were randomized to use continuous glucose monitoring (CGM) as an educational tool to inform decision making and future therapeutic changes; the remaining 33 women were randomized to standard care, study investigator Dr. Helen R. Murphy reported Sept. 8 at the annual meeting of the European Association for the Study of Diabetes.

All statistical analyses were performed on an intention-to-treat basis, said Dr. Murphy of Ipswich (England) Hospital.

At weeks 32–36 of gestation, hemoglobin A_1c levels were significantly lower in the CGM group than in the standard care group (5.8% vs. 6.4%).

In addition, infants born to women in the CGM group were significantly less likely to have a high birth weight than were those born to women in the standard care group. The mean standard deviation (SD) score for birth weight was 0.9 for infants in the CGM group and 1.6 for those in the standard care group.

“What is even more striking is the complete absence of small-for-gestational age babies in women randomized to standard antenatal care,” Dr. Murphy said.

She also noted that there were two infants that had SD scores of above three in the CGM arm, but their mothers had withdrawn from the study before completion.

Compared with children in the standard care arm, the children in the CGM group were at decreased risk (odds ratio 0.36) of macrosomia, defined as a birth weight in the 90th percentile or higher.

CGM was well accepted by the women, according to Dr. Murphy, adding that they wore the monitors on their flank at least once a trimester. The monitors were provided free of charge by Medtronic UK. Ipswich Hospital Diabetes Centre Charity Research Fund and Diabetes UK supported the investigator-led study.

Children in the continuous glucose monitoring group had a 64% lower risk of macrosomia. DR. MURPHY

ROME — Candesartan helped prevent the development of new retinopathy in patients with type 1 diabetes, and prevented worsening eye disease in patients with type 1 and type 2 diabetes, data from an international study program showed. This was true even though the primary end points of the individual studies were not met.

Evidence also suggested that the angiotensin II receptor blocker (ARB) increased the probability of regression of existing eye disease by 34% in patients with type 2 diabetes.

These findings come from the Diabetic Retinopathy Candesartan Trials (DIRECT) program presented at the annual meeting of the European Association for the Study of Diabetes; they are also being published in the Lancet. The findings are the first to show that ARBs could have a direct effect on diabetic retinopathy in normoalbuminuric and normotensive type 1 diabetes patients, or in mildly hypertensive (but treated) type 2 individuals. These data also add to accumulating evidence that these drugs do more than just lower blood pressure.

The finding that candesartan may increase the likelihood of regression in type 2 diabetes is particularly important, since “diabetic eye disease in type 2 patients is very difficult to treat with good effect,” said Dr. Anne Katrin Sjølie, professor of ophthalmology at Odense University Hospital, Denmark. She spoke during a press briefing on the DIRECT program ahead of the formal presentation of the results.

Dr. Sjølie, chair of the DIRECT steering committee that is funded by AstraZeneca and Takeda, noted that the trials program consisted of three randomized controlled studies involving 5,231 patients: DIRECT-PREVENT 1, DIRECT-PROTECT 1, and DIRECT-PROTECT 2. The development or worsening of retinopathy was measured in all these trials as a two- or three-step change on the 11-point Early Treatment of Diabetic Retinopathy Study (ETDRS) scale. This scale uses photographs of the retina to gauge the level and severity of diabetic eye disease.

In DIRECT-PREVENT 1, 711 patients with type 1 diabetes and no existing eye disease were randomized to treatment with candesartan, and another 710 were randomized to placebo. Candesartan reduced the primary end point of the incidence of retinopathy (two-step ETDRS change) by 18% compared with placebo, which was not statistically significant.

However, Dr. Nishi Chaturvedi, professor of clinical epidemiology at Imperial College London, who presented the findings of the DIRECT-PREVENT 1 trial, commented that a significant 35% difference was observed when a three-step change in the ETDRS scale was used in a posttrial analysis. This was largely unaffected by adjustment for baseline diabetes duration and hemoglobin A_1c. “The reason we did this is in order to compare our findings with previous studies to put them into context,” she explained.

Dr. Chaturvedi also showed data from the DIRECT-PROTECT 1 trial, which used a three-step change in the ETDRS scale as its primary end point to see if candesartan could prevent the progression of worsening retinopathy in patients with type 1 diabetes. In this trial there were 951 candesartan- and 954 placebo-treated patients, but no significant difference was seen between the groups in terms of retinopathy progression.

The primary end point of the DIRECT-PROTECT 2 trial also was not met, said Dr. Sjølie, and this was the prevention of worsening retinopathy—again measured by a three-step change in the ETDRS—in patients with type 2 diabetes with existing eye disease, of whom there were 951 treated with the ARB and 954 with placebo. A nonsignificant 13% reduction in retinopathy progression was observed, which did not change greatly when a prespecified adjustment for baseline level of retinopathy, diabetes duration, HbA_1c, urinary albumin excretion rate, systolic blood pressure, or antihypertensive therapy was made. Dr. Sjølie noted, however, there was a 34% improvement in retinopathy regression—a prespecified secondary end point of this study.

In all three studies there were no undue safety concerns, and 80% of the patients given candesartan received a daily dose of 32 mg for 4–6 years, the study sponsors noted in a press release.

Pooled data from the three trials on the effects of candesartan versus placebo on the development of new microalbuminuria were presented by Dr. Rudy Bilous, professor of clinical medicine at the University of Newcastle, England. The data showed no significant benefit of active treatment on this parameter.

The cumulative incidence of microalbuminuria in the trial was small, however, which perhaps reflected the young age of the patients participating in the program. The mean age of patients was approximately 29 years in DIRECT-PREVENT 1, 31 years in DIRECT-PROTECT 1, and 56 years in DIRECT-PREVENT 2.

“We conclude that treatment with candesartan may confer benefit for retinopathy in people with diabetes,” Dr. Bilous said.

“We will never again have such a large study in diabetic retinopathy,” observed Dr. Kristian Hanssen, an independent commentator and professor of medicine at Aker University Hospital in Oslo. He suggested that it probably doesn't matter whether patients use an ARB or an ACE inhibitor; maintaining a low blood pressure—possibly as low as 120/80 mm Hg—is what's important.

“The take-home message is ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy,” Dr. Hanssen said. They should also be considered in those patients with existing eye disease. The study data, together with those from other large-scale studies, should be used to create a “risk engine” to help clinicians diagnose retinopathy in their patients.

Dr. Sjolie, Dr. Chaturvedi, and Dr. Bilous disclosed receiving honoraria to attend DIRECT steering committee meetings from the study program's sponsors, AstraZeneca and Takeda. Dr. Hanssen reported no conflicts of interest.

'ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy.' DR. HANSSEN

ROME — Candesartan helped prevent the development of new retinopathy in patients with type 1 diabetes, and prevented worsening eye disease in patients with type 1 and type 2 diabetes, data from an international study program showed. This was true even though the primary end points of the individual studies were not met.

Evidence also suggested that the angiotensin II receptor blocker (ARB) increased the probability of regression of existing eye disease by 34% in patients with type 2 diabetes.

These findings come from the Diabetic Retinopathy Candesartan Trials (DIRECT) program presented at the annual meeting of the European Association for the Study of Diabetes; they are also being published in the Lancet. The findings are the first to show that ARBs could have a direct effect on diabetic retinopathy in normoalbuminuric and normotensive type 1 diabetes patients, or in mildly hypertensive (but treated) type 2 individuals. These data also add to accumulating evidence that these drugs do more than just lower blood pressure.

The finding that candesartan may increase the likelihood of regression in type 2 diabetes is particularly important, since “diabetic eye disease in type 2 patients is very difficult to treat with good effect,” said Dr. Anne Katrin Sjølie, professor of ophthalmology at Odense University Hospital, Denmark. She spoke during a press briefing on the DIRECT program ahead of the formal presentation of the results.

Dr. Sjølie, chair of the DIRECT steering committee that is funded by AstraZeneca and Takeda, noted that the trials program consisted of three randomized controlled studies involving 5,231 patients: DIRECT-PREVENT 1, DIRECT-PROTECT 1, and DIRECT-PROTECT 2. The development or worsening of retinopathy was measured in all these trials as a two- or three-step change on the 11-point Early Treatment of Diabetic Retinopathy Study (ETDRS) scale. This scale uses photographs of the retina to gauge the level and severity of diabetic eye disease.

In DIRECT-PREVENT 1, 711 patients with type 1 diabetes and no existing eye disease were randomized to treatment with candesartan, and another 710 were randomized to placebo. Candesartan reduced the primary end point of the incidence of retinopathy (two-step ETDRS change) by 18% compared with placebo, which was not statistically significant.

However, Dr. Nishi Chaturvedi, professor of clinical epidemiology at Imperial College London, who presented the findings of the DIRECT-PREVENT 1 trial, commented that a significant 35% difference was observed when a three-step change in the ETDRS scale was used in a posttrial analysis. This was largely unaffected by adjustment for baseline diabetes duration and hemoglobin A_1c. “The reason we did this is in order to compare our findings with previous studies to put them into context,” she explained.

Dr. Chaturvedi also showed data from the DIRECT-PROTECT 1 trial, which used a three-step change in the ETDRS scale as its primary end point to see if candesartan could prevent the progression of worsening retinopathy in patients with type 1 diabetes. In this trial there were 951 candesartan- and 954 placebo-treated patients, but no significant difference was seen between the groups in terms of retinopathy progression.

The primary end point of the DIRECT-PROTECT 2 trial also was not met, said Dr. Sjølie, and this was the prevention of worsening retinopathy—again measured by a three-step change in the ETDRS—in patients with type 2 diabetes with existing eye disease, of whom there were 951 treated with the ARB and 954 with placebo. A nonsignificant 13% reduction in retinopathy progression was observed, which did not change greatly when a prespecified adjustment for baseline level of retinopathy, diabetes duration, HbA_1c, urinary albumin excretion rate, systolic blood pressure, or antihypertensive therapy was made. Dr. Sjølie noted, however, there was a 34% improvement in retinopathy regression—a prespecified secondary end point of this study.

In all three studies there were no undue safety concerns, and 80% of the patients given candesartan received a daily dose of 32 mg for 4–6 years, the study sponsors noted in a press release.

Pooled data from the three trials on the effects of candesartan versus placebo on the development of new microalbuminuria were presented by Dr. Rudy Bilous, professor of clinical medicine at the University of Newcastle, England. The data showed no significant benefit of active treatment on this parameter.

The cumulative incidence of microalbuminuria in the trial was small, however, which perhaps reflected the young age of the patients participating in the program. The mean age of patients was approximately 29 years in DIRECT-PREVENT 1, 31 years in DIRECT-PROTECT 1, and 56 years in DIRECT-PREVENT 2.

“We conclude that treatment with candesartan may confer benefit for retinopathy in people with diabetes,” Dr. Bilous said.

“We will never again have such a large study in diabetic retinopathy,” observed Dr. Kristian Hanssen, an independent commentator and professor of medicine at Aker University Hospital in Oslo. He suggested that it probably doesn't matter whether patients use an ARB or an ACE inhibitor; maintaining a low blood pressure—possibly as low as 120/80 mm Hg—is what's important.

“The take-home message is ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy,” Dr. Hanssen said. They should also be considered in those patients with existing eye disease. The study data, together with those from other large-scale studies, should be used to create a “risk engine” to help clinicians diagnose retinopathy in their patients.

Dr. Sjolie, Dr. Chaturvedi, and Dr. Bilous disclosed receiving honoraria to attend DIRECT steering committee meetings from the study program's sponsors, AstraZeneca and Takeda. Dr. Hanssen reported no conflicts of interest.

'ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy.' DR. HANSSEN

ROME — Candesartan helped prevent the development of new retinopathy in patients with type 1 diabetes, and prevented worsening eye disease in patients with type 1 and type 2 diabetes, data from an international study program showed. This was true even though the primary end points of the individual studies were not met.

Evidence also suggested that the angiotensin II receptor blocker (ARB) increased the probability of regression of existing eye disease by 34% in patients with type 2 diabetes.

These findings come from the Diabetic Retinopathy Candesartan Trials (DIRECT) program presented at the annual meeting of the European Association for the Study of Diabetes; they are also being published in the Lancet. The findings are the first to show that ARBs could have a direct effect on diabetic retinopathy in normoalbuminuric and normotensive type 1 diabetes patients, or in mildly hypertensive (but treated) type 2 individuals. These data also add to accumulating evidence that these drugs do more than just lower blood pressure.

The finding that candesartan may increase the likelihood of regression in type 2 diabetes is particularly important, since “diabetic eye disease in type 2 patients is very difficult to treat with good effect,” said Dr. Anne Katrin Sjølie, professor of ophthalmology at Odense University Hospital, Denmark. She spoke during a press briefing on the DIRECT program ahead of the formal presentation of the results.

Dr. Sjølie, chair of the DIRECT steering committee that is funded by AstraZeneca and Takeda, noted that the trials program consisted of three randomized controlled studies involving 5,231 patients: DIRECT-PREVENT 1, DIRECT-PROTECT 1, and DIRECT-PROTECT 2. The development or worsening of retinopathy was measured in all these trials as a two- or three-step change on the 11-point Early Treatment of Diabetic Retinopathy Study (ETDRS) scale. This scale uses photographs of the retina to gauge the level and severity of diabetic eye disease.

In DIRECT-PREVENT 1, 711 patients with type 1 diabetes and no existing eye disease were randomized to treatment with candesartan, and another 710 were randomized to placebo. Candesartan reduced the primary end point of the incidence of retinopathy (two-step ETDRS change) by 18% compared with placebo, which was not statistically significant.

However, Dr. Nishi Chaturvedi, professor of clinical epidemiology at Imperial College London, who presented the findings of the DIRECT-PREVENT 1 trial, commented that a significant 35% difference was observed when a three-step change in the ETDRS scale was used in a posttrial analysis. This was largely unaffected by adjustment for baseline diabetes duration and hemoglobin A_1c. “The reason we did this is in order to compare our findings with previous studies to put them into context,” she explained.

Dr. Chaturvedi also showed data from the DIRECT-PROTECT 1 trial, which used a three-step change in the ETDRS scale as its primary end point to see if candesartan could prevent the progression of worsening retinopathy in patients with type 1 diabetes. In this trial there were 951 candesartan- and 954 placebo-treated patients, but no significant difference was seen between the groups in terms of retinopathy progression.

The primary end point of the DIRECT-PROTECT 2 trial also was not met, said Dr. Sjølie, and this was the prevention of worsening retinopathy—again measured by a three-step change in the ETDRS—in patients with type 2 diabetes with existing eye disease, of whom there were 951 treated with the ARB and 954 with placebo. A nonsignificant 13% reduction in retinopathy progression was observed, which did not change greatly when a prespecified adjustment for baseline level of retinopathy, diabetes duration, HbA_1c, urinary albumin excretion rate, systolic blood pressure, or antihypertensive therapy was made. Dr. Sjølie noted, however, there was a 34% improvement in retinopathy regression—a prespecified secondary end point of this study.

In all three studies there were no undue safety concerns, and 80% of the patients given candesartan received a daily dose of 32 mg for 4–6 years, the study sponsors noted in a press release.

Pooled data from the three trials on the effects of candesartan versus placebo on the development of new microalbuminuria were presented by Dr. Rudy Bilous, professor of clinical medicine at the University of Newcastle, England. The data showed no significant benefit of active treatment on this parameter.

The cumulative incidence of microalbuminuria in the trial was small, however, which perhaps reflected the young age of the patients participating in the program. The mean age of patients was approximately 29 years in DIRECT-PREVENT 1, 31 years in DIRECT-PROTECT 1, and 56 years in DIRECT-PREVENT 2.

“We conclude that treatment with candesartan may confer benefit for retinopathy in people with diabetes,” Dr. Bilous said.

“We will never again have such a large study in diabetic retinopathy,” observed Dr. Kristian Hanssen, an independent commentator and professor of medicine at Aker University Hospital in Oslo. He suggested that it probably doesn't matter whether patients use an ARB or an ACE inhibitor; maintaining a low blood pressure—possibly as low as 120/80 mm Hg—is what's important.

“The take-home message is ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy,” Dr. Hanssen said. They should also be considered in those patients with existing eye disease. The study data, together with those from other large-scale studies, should be used to create a “risk engine” to help clinicians diagnose retinopathy in their patients.

Dr. Sjolie, Dr. Chaturvedi, and Dr. Bilous disclosed receiving honoraria to attend DIRECT steering committee meetings from the study program's sponsors, AstraZeneca and Takeda. Dr. Hanssen reported no conflicts of interest.

'ARBs or ACE inhibitors are indicated in patients with risk of progression into retinopathy.' DR. HANSSEN