Fran Lowry

Steroids may prevent or reverse the desensitization occurring with prolonged exposure to short-acting β₂-adrenergic receptor agonists in treating chronic obstructive pulmonary disease and asthma.

Phillip R. Cooper, Ph.D., and Dr. Reynold A. Panettieri Jr. incubated slices of human lung tissue containing small airways with the short-acting β₂-adrenergic receptor agonist albuterol for 3, 6, or 12 hours at different concentrations. The incubation weakened subsequent isoproterenol-induced relaxation in a dose- and time-dependent manner (J. Allergy Clin. Immunol. 2008 Sept. 9 [doi: 10.1016/j.jaci.2 008.07. 040]).

After 12 hours of albuterol incubation, they noted a 40% decrease in maximum relaxation and a 45% decrease in airway sensitivity, compared with control values. The differences were statistically significant. In contrast, preincubating the slices of lung tissue with dexamethasone for 1 hour prevented the albuterol-induced desensitization. A 30-minute dexamethasone incubation didn't change albuterol-induced desensitization.

This is the first study to demonstrate a model of β₂-adrenergic receptor tolerance in human small airways. It provides a platform to determine the exact mechanisms of β-agonist desensitization in humans, as well as ways of preventing tolerance to those agonists in human airway disease. The take-home message is that steroids can reverse that tolerance, said the authors. They said they had no conflicts of interest.

Steroids may prevent or reverse the desensitization occurring with prolonged exposure to short-acting β₂-adrenergic receptor agonists in treating chronic obstructive pulmonary disease and asthma.

Phillip R. Cooper, Ph.D., and Dr. Reynold A. Panettieri Jr. incubated slices of human lung tissue containing small airways with the short-acting β₂-adrenergic receptor agonist albuterol for 3, 6, or 12 hours at different concentrations. The incubation weakened subsequent isoproterenol-induced relaxation in a dose- and time-dependent manner (J. Allergy Clin. Immunol. 2008 Sept. 9 [doi: 10.1016/j.jaci.2 008.07. 040]).

After 12 hours of albuterol incubation, they noted a 40% decrease in maximum relaxation and a 45% decrease in airway sensitivity, compared with control values. The differences were statistically significant. In contrast, preincubating the slices of lung tissue with dexamethasone for 1 hour prevented the albuterol-induced desensitization. A 30-minute dexamethasone incubation didn't change albuterol-induced desensitization.

This is the first study to demonstrate a model of β₂-adrenergic receptor tolerance in human small airways. It provides a platform to determine the exact mechanisms of β-agonist desensitization in humans, as well as ways of preventing tolerance to those agonists in human airway disease. The take-home message is that steroids can reverse that tolerance, said the authors. They said they had no conflicts of interest.

Steroids may prevent or reverse the desensitization occurring with prolonged exposure to short-acting β₂-adrenergic receptor agonists in treating chronic obstructive pulmonary disease and asthma.

Phillip R. Cooper, Ph.D., and Dr. Reynold A. Panettieri Jr. incubated slices of human lung tissue containing small airways with the short-acting β₂-adrenergic receptor agonist albuterol for 3, 6, or 12 hours at different concentrations. The incubation weakened subsequent isoproterenol-induced relaxation in a dose- and time-dependent manner (J. Allergy Clin. Immunol. 2008 Sept. 9 [doi: 10.1016/j.jaci.2 008.07. 040]).

After 12 hours of albuterol incubation, they noted a 40% decrease in maximum relaxation and a 45% decrease in airway sensitivity, compared with control values. The differences were statistically significant. In contrast, preincubating the slices of lung tissue with dexamethasone for 1 hour prevented the albuterol-induced desensitization. A 30-minute dexamethasone incubation didn't change albuterol-induced desensitization.

This is the first study to demonstrate a model of β₂-adrenergic receptor tolerance in human small airways. It provides a platform to determine the exact mechanisms of β-agonist desensitization in humans, as well as ways of preventing tolerance to those agonists in human airway disease. The take-home message is that steroids can reverse that tolerance, said the authors. They said they had no conflicts of interest.

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing, which were also reviewed—in reducing depressive disorders, posttraumatic stress disorder (PTSD), anxiety and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

For the report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing (Am. J. Prev. Med. 2008;35:287–313).

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high. It is important that physicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” he said.

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The task force recommended that children and teens be screened, lest their trauma symptoms go undetected. The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education.

It is important that physicians treat these children appropriately, with therapy that is effective. DR. HAHN

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing, which were also reviewed—in reducing depressive disorders, posttraumatic stress disorder (PTSD), anxiety and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

For the report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing (Am. J. Prev. Med. 2008;35:287–313).

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high. It is important that physicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” he said.

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The task force recommended that children and teens be screened, lest their trauma symptoms go undetected. The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education.

It is important that physicians treat these children appropriately, with therapy that is effective. DR. HAHN

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing, which were also reviewed—in reducing depressive disorders, posttraumatic stress disorder (PTSD), anxiety and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

For the report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing (Am. J. Prev. Med. 2008;35:287–313).

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high. It is important that physicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” he said.

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The task force recommended that children and teens be screened, lest their trauma symptoms go undetected. The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education.

It is important that physicians treat these children appropriately, with therapy that is effective. DR. HAHN

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing–the other interventions that were reviewed–in reducing depressive disorders, anxiety, posttraumatic stress disorder (PTSD), and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

“Children and adolescents in the United States and worldwide are commonly exposed to traumatic events, yet practitioners treating these young people to reduce subsequent psychological harm may not be aware of–or use–interventions based on the best available evidence,” the authors wrote (Am. J. Prev. Med. 2008;35:287-313). The task force is a project that has been in place since 1995. Funded by the CDC and the Department of Health and Human Services, it reviews major interventions in multiple arenas of public health–such as tobacco control, motor vehicle safety, sexual behavior, diabetes control, and mental health–to determine what measures work, what might be harmful, and what areas need new research.

For this report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing.

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high.

Not all children will go on to experience harmful psychological consequences, but a proportion will, and this can lead to risky behaviors–such as smoking, drinking, and criminal behavior–in the adult years, he said in an interview.

It is important that clinicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” said Dr. Hahn, who is also coordinating scientist for the violence prevention review team and the excessive alcohol prevention review team at the CDC.

One of the interventions reviewed, psychological debriefing, may even be harmful, Dr. Hahn noted. “This has been found to have some harm, at least in adults, because it is administered to people in a group, right after an event, whether they have symptoms or not. They sit around in a group and listen to each other's traumatic experience, so in a sense they are exposed to another version of the trauma they themselves suffered. This psychological debriefing may not provide an opportunity for them to get referrals and subsequent treatment, and we therefore urge caution and more research [regarding this intervention] in children and adolescents.”

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education. No other financial disclosures were reported by the authors of the report.

The evidence was lacking for all the other interventions reviewed, even for pharmaceutical therapy. DR. HAHN

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing–the other interventions that were reviewed–in reducing depressive disorders, anxiety, posttraumatic stress disorder (PTSD), and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

“Children and adolescents in the United States and worldwide are commonly exposed to traumatic events, yet practitioners treating these young people to reduce subsequent psychological harm may not be aware of–or use–interventions based on the best available evidence,” the authors wrote (Am. J. Prev. Med. 2008;35:287-313). The task force is a project that has been in place since 1995. Funded by the CDC and the Department of Health and Human Services, it reviews major interventions in multiple arenas of public health–such as tobacco control, motor vehicle safety, sexual behavior, diabetes control, and mental health–to determine what measures work, what might be harmful, and what areas need new research.

For this report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing.

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high.

Not all children will go on to experience harmful psychological consequences, but a proportion will, and this can lead to risky behaviors–such as smoking, drinking, and criminal behavior–in the adult years, he said in an interview.

It is important that clinicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” said Dr. Hahn, who is also coordinating scientist for the violence prevention review team and the excessive alcohol prevention review team at the CDC.

One of the interventions reviewed, psychological debriefing, may even be harmful, Dr. Hahn noted. “This has been found to have some harm, at least in adults, because it is administered to people in a group, right after an event, whether they have symptoms or not. They sit around in a group and listen to each other's traumatic experience, so in a sense they are exposed to another version of the trauma they themselves suffered. This psychological debriefing may not provide an opportunity for them to get referrals and subsequent treatment, and we therefore urge caution and more research [regarding this intervention] in children and adolescents.”

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education. No other financial disclosures were reported by the authors of the report.

The evidence was lacking for all the other interventions reviewed, even for pharmaceutical therapy. DR. HAHN

Only cognitive-behavioral therapy, of all the major interventions being used to reduce psychological harm in children and adolescents who have witnessed or been victims of trauma or violence, has strong evidence to show it is effective, according to a review.

Evidence was scant for the effectiveness of play therapy, art therapy, psychodynamic therapy, pharmacologic therapy, or psychological debriefing–the other interventions that were reviewed–in reducing depressive disorders, anxiety, posttraumatic stress disorder (PTSD), and other adverse sequelae in this population, said Holly R. Wethington, Ph.D., and associates of the task force on community preventive services at the Centers for Disease Control and Prevention.

“Children and adolescents in the United States and worldwide are commonly exposed to traumatic events, yet practitioners treating these young people to reduce subsequent psychological harm may not be aware of–or use–interventions based on the best available evidence,” the authors wrote (Am. J. Prev. Med. 2008;35:287-313). The task force is a project that has been in place since 1995. Funded by the CDC and the Department of Health and Human Services, it reviews major interventions in multiple arenas of public health–such as tobacco control, motor vehicle safety, sexual behavior, diabetes control, and mental health–to determine what measures work, what might be harmful, and what areas need new research.

For this report, electronic searches for literature used databases including Medline and PsycINFO, and looked for articles written in English on the particular treatments up to March 2007. Types of trauma included physical or sexual abuse, community violence, suicide of a family member, juvenile cancer and treatment, traffic accidents, and natural disasters. Eleven studies were deemed appropriate for consideration for individual cognitive-behavioral therapy (CBT) and 10 for group CBT. Four studies were identified for play therapy, one for art therapy, two each for psychodynamic and pharmacologic therapy, and one for psychological debriefing.

Task force member Robert A. Hahn, Ph.D., said that children and adolescents in the United States are exposed to multiple trauma rates that were surprising to him because they were so high.

Not all children will go on to experience harmful psychological consequences, but a proportion will, and this can lead to risky behaviors–such as smoking, drinking, and criminal behavior–in the adult years, he said in an interview.

It is important that clinicians treat these children appropriately, with therapy that is effective. “Except for cognitive-behavioral therapy, the evidence was lacking for all the other interventions we reviewed, even for pharmaceutical therapy, which is important because it is used by many psychiatrists,” said Dr. Hahn, who is also coordinating scientist for the violence prevention review team and the excessive alcohol prevention review team at the CDC.

One of the interventions reviewed, psychological debriefing, may even be harmful, Dr. Hahn noted. “This has been found to have some harm, at least in adults, because it is administered to people in a group, right after an event, whether they have symptoms or not. They sit around in a group and listen to each other's traumatic experience, so in a sense they are exposed to another version of the trauma they themselves suffered. This psychological debriefing may not provide an opportunity for them to get referrals and subsequent treatment, and we therefore urge caution and more research [regarding this intervention] in children and adolescents.”

A “major challenge is that children and adolescents who have been traumatized and may need treatment for PTSD or other psychological conditions generally do not receive that treatment,” according to the task force.

The work of Dr. Wethington and two other members of the task force was supported by funding from the Oak Ridge Institute for Science and Education. No other financial disclosures were reported by the authors of the report.

The evidence was lacking for all the other interventions reviewed, even for pharmaceutical therapy. DR. HAHN

Influenza vaccination was not associated with a significantly reduced risk of community-acquired pneumonia in people aged 65 and older, according to the results of a population-based study.

In the study of 1,173 cases and 2,346 controls, flu vaccine was associated with an 8% lower risk of community-acquired pneumonia among immunocompetent seniors during influenza season.

The finding stands in contrast to a number of observational studies that suggest that vaccination substantially reduces the risk of hospital admission due to pneumonia in elderly adults. But these studies have not differentiated between healthy, mobile, immunocompetent seniors and frail seniors of advanced age or seniors with severe comorbidities or chronic health conditions, who are known to benefit from influenza vaccine. As a result, these studies have overestimated how well the vaccine actually works in older individuals in general, the investigators wrote.

To challenge these observations, they conducted a nested case-control study of immunocompetent individuals aged 65–94 years who were enrolled in Group Health, a health maintenance organization in Seattle, during 2000, 2001, and 2002.

To ensure that they were removing any bias in their results, the researchers looked at both the preinfluenza and influenza periods of each year, reasoning that any benefit from the flu vaccine that was seen in the preinfluenza season could not be due to the protective effects of the vaccine.

They found that in the preinfluenza season, there was an apparent strong benefit of the vaccine, with a 40% reduction in the risk of pneumonia. But after controlling for the presence of frail and sick seniors, they found essentially no effect of influenza vaccine during preinfluenza periods, reported the researchers, led by Michael L. Jackson, Ph.D., of the Group Health Center for Health Studies, Seattle (Lancet 2008;372:398-405).

They then looked at the effect of the flu vaccine during influenza periods. Before they did so, they selected subjects who were immunocompetent and had no serious comorbidities, based on a careful scrutiny of the subjects' medical records.

The age- and sex-adjusted odds ratio for the association between influenza vaccination and risk of community-acquired pneumonia was 1.04, but after adjustment for the confounding factors that were identified in the preinfluenza periods, the influenza season odds ratio was 0.92.

In an interview, Dr. Jackson said that the findings are consistent with there being no link between flu vaccine and pneumonia risk in seniors. However, this does not mean that the elderly should forego their annual flu shot.

“Randomized trials, which are the gold standard for public health-related evidence, have found that influenza vaccine reduces the risk of influenza infection in young—that is, 75 years and younger—healthy seniors. So they should still get their flu shots,” he said.

He added that more work needs to be done to understand how well the vaccine prevents serious complications of the flu, such as pneumonia, in older seniors and those with chronic health problems.

In an accompanying editorial, Dr. Edward A. Belongia of the Marshfield (Wis.) Clinic Research Foundation, and Dr. David K. Shay of the influenza division, Centers for Disease Control and Prevention, agreed with the need for additional studies about the causes of pneumonia in elderly adults, particularly in highly vaccinated populations (Lancet 2008;372:352-4).

Calling the study by Dr. Jackson and his colleagues “well designed,” they added that standard methods of comparing the effectiveness of flu shots in different seasons and in different populations are also needed.

The commentators also suggested that future studies of vaccine effectiveness should include other flu-related acute illnesses besides pneumonia and use sensitive and specific diagnostic tests, such as the polymerase chain reaction, for influenza.

“More studies that use laboratory-confirmed outcomes and adjust for a broad range of confounding variables will provide valuable information about the effects of antigenic match and other factors that affect vaccine effectiveness,” they wrote.

One of the authors of the study disclosed she is a paid consultant to Sanofi Pasteur and to Novartis, manufacturers of the influenza vaccine. The other authors declared they had no conflict of interest.

Influenza vaccination was not associated with a significantly reduced risk of community-acquired pneumonia in people aged 65 and older, according to the results of a population-based study.

In the study of 1,173 cases and 2,346 controls, flu vaccine was associated with an 8% lower risk of community-acquired pneumonia among immunocompetent seniors during influenza season.

The finding stands in contrast to a number of observational studies that suggest that vaccination substantially reduces the risk of hospital admission due to pneumonia in elderly adults. But these studies have not differentiated between healthy, mobile, immunocompetent seniors and frail seniors of advanced age or seniors with severe comorbidities or chronic health conditions, who are known to benefit from influenza vaccine. As a result, these studies have overestimated how well the vaccine actually works in older individuals in general, the investigators wrote.

To challenge these observations, they conducted a nested case-control study of immunocompetent individuals aged 65–94 years who were enrolled in Group Health, a health maintenance organization in Seattle, during 2000, 2001, and 2002.

To ensure that they were removing any bias in their results, the researchers looked at both the preinfluenza and influenza periods of each year, reasoning that any benefit from the flu vaccine that was seen in the preinfluenza season could not be due to the protective effects of the vaccine.

They found that in the preinfluenza season, there was an apparent strong benefit of the vaccine, with a 40% reduction in the risk of pneumonia. But after controlling for the presence of frail and sick seniors, they found essentially no effect of influenza vaccine during preinfluenza periods, reported the researchers, led by Michael L. Jackson, Ph.D., of the Group Health Center for Health Studies, Seattle (Lancet 2008;372:398-405).

They then looked at the effect of the flu vaccine during influenza periods. Before they did so, they selected subjects who were immunocompetent and had no serious comorbidities, based on a careful scrutiny of the subjects' medical records.

The age- and sex-adjusted odds ratio for the association between influenza vaccination and risk of community-acquired pneumonia was 1.04, but after adjustment for the confounding factors that were identified in the preinfluenza periods, the influenza season odds ratio was 0.92.

In an interview, Dr. Jackson said that the findings are consistent with there being no link between flu vaccine and pneumonia risk in seniors. However, this does not mean that the elderly should forego their annual flu shot.

“Randomized trials, which are the gold standard for public health-related evidence, have found that influenza vaccine reduces the risk of influenza infection in young—that is, 75 years and younger—healthy seniors. So they should still get their flu shots,” he said.

He added that more work needs to be done to understand how well the vaccine prevents serious complications of the flu, such as pneumonia, in older seniors and those with chronic health problems.

In an accompanying editorial, Dr. Edward A. Belongia of the Marshfield (Wis.) Clinic Research Foundation, and Dr. David K. Shay of the influenza division, Centers for Disease Control and Prevention, agreed with the need for additional studies about the causes of pneumonia in elderly adults, particularly in highly vaccinated populations (Lancet 2008;372:352-4).

Calling the study by Dr. Jackson and his colleagues “well designed,” they added that standard methods of comparing the effectiveness of flu shots in different seasons and in different populations are also needed.

The commentators also suggested that future studies of vaccine effectiveness should include other flu-related acute illnesses besides pneumonia and use sensitive and specific diagnostic tests, such as the polymerase chain reaction, for influenza.

“More studies that use laboratory-confirmed outcomes and adjust for a broad range of confounding variables will provide valuable information about the effects of antigenic match and other factors that affect vaccine effectiveness,” they wrote.

One of the authors of the study disclosed she is a paid consultant to Sanofi Pasteur and to Novartis, manufacturers of the influenza vaccine. The other authors declared they had no conflict of interest.

Influenza vaccination was not associated with a significantly reduced risk of community-acquired pneumonia in people aged 65 and older, according to the results of a population-based study.

In the study of 1,173 cases and 2,346 controls, flu vaccine was associated with an 8% lower risk of community-acquired pneumonia among immunocompetent seniors during influenza season.

The finding stands in contrast to a number of observational studies that suggest that vaccination substantially reduces the risk of hospital admission due to pneumonia in elderly adults. But these studies have not differentiated between healthy, mobile, immunocompetent seniors and frail seniors of advanced age or seniors with severe comorbidities or chronic health conditions, who are known to benefit from influenza vaccine. As a result, these studies have overestimated how well the vaccine actually works in older individuals in general, the investigators wrote.

To challenge these observations, they conducted a nested case-control study of immunocompetent individuals aged 65–94 years who were enrolled in Group Health, a health maintenance organization in Seattle, during 2000, 2001, and 2002.

To ensure that they were removing any bias in their results, the researchers looked at both the preinfluenza and influenza periods of each year, reasoning that any benefit from the flu vaccine that was seen in the preinfluenza season could not be due to the protective effects of the vaccine.

They found that in the preinfluenza season, there was an apparent strong benefit of the vaccine, with a 40% reduction in the risk of pneumonia. But after controlling for the presence of frail and sick seniors, they found essentially no effect of influenza vaccine during preinfluenza periods, reported the researchers, led by Michael L. Jackson, Ph.D., of the Group Health Center for Health Studies, Seattle (Lancet 2008;372:398-405).

They then looked at the effect of the flu vaccine during influenza periods. Before they did so, they selected subjects who were immunocompetent and had no serious comorbidities, based on a careful scrutiny of the subjects' medical records.

The age- and sex-adjusted odds ratio for the association between influenza vaccination and risk of community-acquired pneumonia was 1.04, but after adjustment for the confounding factors that were identified in the preinfluenza periods, the influenza season odds ratio was 0.92.

In an interview, Dr. Jackson said that the findings are consistent with there being no link between flu vaccine and pneumonia risk in seniors. However, this does not mean that the elderly should forego their annual flu shot.

“Randomized trials, which are the gold standard for public health-related evidence, have found that influenza vaccine reduces the risk of influenza infection in young—that is, 75 years and younger—healthy seniors. So they should still get their flu shots,” he said.

He added that more work needs to be done to understand how well the vaccine prevents serious complications of the flu, such as pneumonia, in older seniors and those with chronic health problems.

In an accompanying editorial, Dr. Edward A. Belongia of the Marshfield (Wis.) Clinic Research Foundation, and Dr. David K. Shay of the influenza division, Centers for Disease Control and Prevention, agreed with the need for additional studies about the causes of pneumonia in elderly adults, particularly in highly vaccinated populations (Lancet 2008;372:352-4).

Calling the study by Dr. Jackson and his colleagues “well designed,” they added that standard methods of comparing the effectiveness of flu shots in different seasons and in different populations are also needed.

The commentators also suggested that future studies of vaccine effectiveness should include other flu-related acute illnesses besides pneumonia and use sensitive and specific diagnostic tests, such as the polymerase chain reaction, for influenza.

“More studies that use laboratory-confirmed outcomes and adjust for a broad range of confounding variables will provide valuable information about the effects of antigenic match and other factors that affect vaccine effectiveness,” they wrote.

One of the authors of the study disclosed she is a paid consultant to Sanofi Pasteur and to Novartis, manufacturers of the influenza vaccine. The other authors declared they had no conflict of interest.

CHICAGO — Two retrospective studies presented at the annual meeting of the American Society of Clinical Oncology show that changes in hormone- and HER2-receptor status are indeed possible between primary and recurrent breast cancer lesions, and that survival outcomes are severely compromised when they occur.

In one study, Dr. Robyn MacFarlane of the University of British Columbia, Vancouver, reported that 30 of 160 patients (19%) had changes in estrogen-receptor (ER), progesterone-receptor (PR), or human epidermal growth factor receptor 2 (HER2)-receptor status when their relapsed or metastatic tumor was compared with their primary tumor.

In the second study, Dr. Cornelia Liedtke of the Westfälische Wilhelms-Universität Münster (Germany) reported that change in receptor status was associated with a much shorter survival after recurrence, as compared with no change.

In her study, 176 patients with triple-negative breast cancer had recurring tumors with the same receptor status as their primary tumors. They had a mean overall survival of 43 months, compared with just 16 months for 55 patients whose original triple-negative tumors converted to positive receptor status when they recurred.

Dr. MacFarlane said she and her coauthors were prompted to conduct their study by three earlier reports that suggested a significant proportion of relapsed lesions may have changes in hormone-receptor and HER2-receptor status from the original tumor.

When the researchers analyzed their tissue samples, they found changes—from positive to negative and vice versa—in ER-, PR-, and HER2-receptor status. None of the changes was related to treatment of the primary tumor, Dr. MacFarlane reported.

“These changes have implications for selection of treatment options of relapsed breast cancers, and we think that the findings illustrate the need for a rebiopsy, if feasible, at the time of relapse or recurrence to determine if there has been any change in the hormone-receptor and HER2-receptor status,” she said.

Dr. Liedtke, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston, and her coinvestigators performed a retrospective chart review of 789 patients enrolled in M.D. Anderson's institutional breast cancer database between 1982 and 2006.

The researchers identified 231 patients who had triple-negative breast cancer (defined as no ER, PR, or HER2 expression). Of these triple-negative patients, 55 developed non-triple-negative tumors (defined as positive for at least one ER, PR, or HER2 receptor) at recurrence. These patients' overall survival was significantly worse than that of their counterparts who recurred with triple-negative status tumors.

In a discussion of the studies, Dr. Paul E. Goss commended Dr. MacFarlane and Dr. Liedtke for introducing a topic of extreme importance to physicians who care for breast cancer patients. Dr. Goss, professor of medicine at Harvard Medical School and director of breast cancer research at Massachusetts General Hospital, both in Boston, noted that both studies showed about a 20% rate of migration of receptors from primary to recurrent lesions, and that this change meant a worsening of outcome.

He asked that clinicians in the audience start to collect metastatic biopsies prospectively. “We need planned metastatic biopsies in ongoing clinical trials. I would ask you to rigorously persuade patients to allow biopsies of their recurrent tumors, so that we can correlate biologic findings to response to treatments and clinical outcomes,” he said.

Neither Dr. MacFarlane nor Dr. Liedtke reported any conflicts of interest.

Dr. Goss disclosed relationships with Novartis, Pfizer Inc., AstraZeneca Pharmaceuticals LP, and GlaxoSmithKline Inc.

'We need planned metastatic biopsies in ongoing clinical trials.' DR. GOSS

CHICAGO — Two retrospective studies presented at the annual meeting of the American Society of Clinical Oncology show that changes in hormone- and HER2-receptor status are indeed possible between primary and recurrent breast cancer lesions, and that survival outcomes are severely compromised when they occur.

In one study, Dr. Robyn MacFarlane of the University of British Columbia, Vancouver, reported that 30 of 160 patients (19%) had changes in estrogen-receptor (ER), progesterone-receptor (PR), or human epidermal growth factor receptor 2 (HER2)-receptor status when their relapsed or metastatic tumor was compared with their primary tumor.

In the second study, Dr. Cornelia Liedtke of the Westfälische Wilhelms-Universität Münster (Germany) reported that change in receptor status was associated with a much shorter survival after recurrence, as compared with no change.

In her study, 176 patients with triple-negative breast cancer had recurring tumors with the same receptor status as their primary tumors. They had a mean overall survival of 43 months, compared with just 16 months for 55 patients whose original triple-negative tumors converted to positive receptor status when they recurred.

Dr. MacFarlane said she and her coauthors were prompted to conduct their study by three earlier reports that suggested a significant proportion of relapsed lesions may have changes in hormone-receptor and HER2-receptor status from the original tumor.

When the researchers analyzed their tissue samples, they found changes—from positive to negative and vice versa—in ER-, PR-, and HER2-receptor status. None of the changes was related to treatment of the primary tumor, Dr. MacFarlane reported.

“These changes have implications for selection of treatment options of relapsed breast cancers, and we think that the findings illustrate the need for a rebiopsy, if feasible, at the time of relapse or recurrence to determine if there has been any change in the hormone-receptor and HER2-receptor status,” she said.

Dr. Liedtke, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston, and her coinvestigators performed a retrospective chart review of 789 patients enrolled in M.D. Anderson's institutional breast cancer database between 1982 and 2006.

The researchers identified 231 patients who had triple-negative breast cancer (defined as no ER, PR, or HER2 expression). Of these triple-negative patients, 55 developed non-triple-negative tumors (defined as positive for at least one ER, PR, or HER2 receptor) at recurrence. These patients' overall survival was significantly worse than that of their counterparts who recurred with triple-negative status tumors.

In a discussion of the studies, Dr. Paul E. Goss commended Dr. MacFarlane and Dr. Liedtke for introducing a topic of extreme importance to physicians who care for breast cancer patients. Dr. Goss, professor of medicine at Harvard Medical School and director of breast cancer research at Massachusetts General Hospital, both in Boston, noted that both studies showed about a 20% rate of migration of receptors from primary to recurrent lesions, and that this change meant a worsening of outcome.

He asked that clinicians in the audience start to collect metastatic biopsies prospectively. “We need planned metastatic biopsies in ongoing clinical trials. I would ask you to rigorously persuade patients to allow biopsies of their recurrent tumors, so that we can correlate biologic findings to response to treatments and clinical outcomes,” he said.

Neither Dr. MacFarlane nor Dr. Liedtke reported any conflicts of interest.

Dr. Goss disclosed relationships with Novartis, Pfizer Inc., AstraZeneca Pharmaceuticals LP, and GlaxoSmithKline Inc.

'We need planned metastatic biopsies in ongoing clinical trials.' DR. GOSS

CHICAGO — Two retrospective studies presented at the annual meeting of the American Society of Clinical Oncology show that changes in hormone- and HER2-receptor status are indeed possible between primary and recurrent breast cancer lesions, and that survival outcomes are severely compromised when they occur.

In one study, Dr. Robyn MacFarlane of the University of British Columbia, Vancouver, reported that 30 of 160 patients (19%) had changes in estrogen-receptor (ER), progesterone-receptor (PR), or human epidermal growth factor receptor 2 (HER2)-receptor status when their relapsed or metastatic tumor was compared with their primary tumor.

In the second study, Dr. Cornelia Liedtke of the Westfälische Wilhelms-Universität Münster (Germany) reported that change in receptor status was associated with a much shorter survival after recurrence, as compared with no change.

In her study, 176 patients with triple-negative breast cancer had recurring tumors with the same receptor status as their primary tumors. They had a mean overall survival of 43 months, compared with just 16 months for 55 patients whose original triple-negative tumors converted to positive receptor status when they recurred.

Dr. MacFarlane said she and her coauthors were prompted to conduct their study by three earlier reports that suggested a significant proportion of relapsed lesions may have changes in hormone-receptor and HER2-receptor status from the original tumor.

When the researchers analyzed their tissue samples, they found changes—from positive to negative and vice versa—in ER-, PR-, and HER2-receptor status. None of the changes was related to treatment of the primary tumor, Dr. MacFarlane reported.

“These changes have implications for selection of treatment options of relapsed breast cancers, and we think that the findings illustrate the need for a rebiopsy, if feasible, at the time of relapse or recurrence to determine if there has been any change in the hormone-receptor and HER2-receptor status,” she said.

Dr. Liedtke, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston, and her coinvestigators performed a retrospective chart review of 789 patients enrolled in M.D. Anderson's institutional breast cancer database between 1982 and 2006.

The researchers identified 231 patients who had triple-negative breast cancer (defined as no ER, PR, or HER2 expression). Of these triple-negative patients, 55 developed non-triple-negative tumors (defined as positive for at least one ER, PR, or HER2 receptor) at recurrence. These patients' overall survival was significantly worse than that of their counterparts who recurred with triple-negative status tumors.

In a discussion of the studies, Dr. Paul E. Goss commended Dr. MacFarlane and Dr. Liedtke for introducing a topic of extreme importance to physicians who care for breast cancer patients. Dr. Goss, professor of medicine at Harvard Medical School and director of breast cancer research at Massachusetts General Hospital, both in Boston, noted that both studies showed about a 20% rate of migration of receptors from primary to recurrent lesions, and that this change meant a worsening of outcome.

He asked that clinicians in the audience start to collect metastatic biopsies prospectively. “We need planned metastatic biopsies in ongoing clinical trials. I would ask you to rigorously persuade patients to allow biopsies of their recurrent tumors, so that we can correlate biologic findings to response to treatments and clinical outcomes,” he said.

Neither Dr. MacFarlane nor Dr. Liedtke reported any conflicts of interest.

Dr. Goss disclosed relationships with Novartis, Pfizer Inc., AstraZeneca Pharmaceuticals LP, and GlaxoSmithKline Inc.

'We need planned metastatic biopsies in ongoing clinical trials.' DR. GOSS

CHICAGO — The treatment for pediatric cancers is becoming more successful, but at a price—increased incidences of new primary sarcomas and female infertility, according to two reports by the Childhood Cancer Survivor Study presented at the American Society of Clinical Oncology.

Exposure to radiation at doses over 10 Gy was the most important risk factor for the development of new sarcomas in childhood cancer survivors, said Dr. Tara O. Henderson of the University of Chicago.

Overall, radiation treatment was associated with an odds ratio of 4.7 for the development of a subsequent primary sarcoma. In patients who received more than 50 Gy, the odds ratio jumped to 31.6, Dr. Henderson reported.

The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study in 27 institutions in the United States and Canada. It includes 5-year survivors of leukemia, lymphoma, CNS cancer, bone cancer, Wilms' tumor, neuroblastoma, or soft-tissue sarcoma diagnosed between 1978 and 1986, with diagnoses at less than age 21 years.

Dr. Henderson and her associates found 127 confirmed sarcomas in a cohort of 14,372 survivors. Each case was matched by age, sex, and time since primary cancer diagnosis with four CCSS cohort members without subsequent sarcomas.

Radiation doses at the site of the subsequent sarcoma were estimated by medical physicists at the University of Texas M.D. Anderson Cancer Center, Houston, and chemotherapy information was obtained from patients' medical records.

Sarcomas occurred a median of 13 years (range 5-33 years) from the original cancer diagnosis.

Exposure to certain chemotherapy agents was also associated with risk for subsequent sarcomas. For anthracyclines, the odds ratio was 2.5; for bleomycin 4.6, and for alkylators 1.9.

In the second CCSS study, Dr. Daniel M. Green, of St. Jude Children's Research Hospital in Memphis, Tenn., reported that adult female survivors of childhood cancer were significantly less likely to have ever been pregnant, compared with their female siblings who did not have cancer.

Of the 5,149 survivors, 1,506 (29%) had ever achieved pregnancy, compared with 613 of the 1,441 siblings (43%) (relative risk, 0.81).

The risk of ever being pregnant decreased as the maximum ovarian/uterine radiation dose increased. Radiation doses greater than 1,500 cGy were associated with a greater than fivefold increased risk of not having been pregnant, Dr. Green reported.

The investigators also looked at chemotherapy agents and found that alkylator and cyclophosphamide exposure was significantly associated with less likelihood of pregnancy in a dose-dependent manner.

In her discussion of these studies, Dr. Smita Bhatia of City of Hope National Medical Center in Duarte, Calif., said they highlight a critical need to increase awareness of the health problems faced by childhood cancer survivors—not only among the survivors themselves, but also among the primary physicians who provide most of their care.

One-third of childhood cancer survivors will have a life threatening complication 30 years out from diagnosis and treatment of their cancer, she said, citing a recent study (N. Engl. J. Med. 2006;355:1572-82).

“Primary cancer will continue to be treated with intense therapeutic exposure, and invariably will result in late effects. We need to focus on genetic predispositions and other factors which contribute toward these late effects, so that we can identify high-risk populations, and screen them appropriately to prevent these complications from happening and decrease the morbidity and mortality associated with late events,” she said.

Dr. Henderson, Dr. Green, and Dr. Bhatia all stated that they had no conflicts of interest to report.

CHICAGO — The treatment for pediatric cancers is becoming more successful, but at a price—increased incidences of new primary sarcomas and female infertility, according to two reports by the Childhood Cancer Survivor Study presented at the American Society of Clinical Oncology.

Exposure to radiation at doses over 10 Gy was the most important risk factor for the development of new sarcomas in childhood cancer survivors, said Dr. Tara O. Henderson of the University of Chicago.

Overall, radiation treatment was associated with an odds ratio of 4.7 for the development of a subsequent primary sarcoma. In patients who received more than 50 Gy, the odds ratio jumped to 31.6, Dr. Henderson reported.

The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study in 27 institutions in the United States and Canada. It includes 5-year survivors of leukemia, lymphoma, CNS cancer, bone cancer, Wilms' tumor, neuroblastoma, or soft-tissue sarcoma diagnosed between 1978 and 1986, with diagnoses at less than age 21 years.

Dr. Henderson and her associates found 127 confirmed sarcomas in a cohort of 14,372 survivors. Each case was matched by age, sex, and time since primary cancer diagnosis with four CCSS cohort members without subsequent sarcomas.

Radiation doses at the site of the subsequent sarcoma were estimated by medical physicists at the University of Texas M.D. Anderson Cancer Center, Houston, and chemotherapy information was obtained from patients' medical records.

Sarcomas occurred a median of 13 years (range 5-33 years) from the original cancer diagnosis.

Exposure to certain chemotherapy agents was also associated with risk for subsequent sarcomas. For anthracyclines, the odds ratio was 2.5; for bleomycin 4.6, and for alkylators 1.9.

In the second CCSS study, Dr. Daniel M. Green, of St. Jude Children's Research Hospital in Memphis, Tenn., reported that adult female survivors of childhood cancer were significantly less likely to have ever been pregnant, compared with their female siblings who did not have cancer.

Of the 5,149 survivors, 1,506 (29%) had ever achieved pregnancy, compared with 613 of the 1,441 siblings (43%) (relative risk, 0.81).

The risk of ever being pregnant decreased as the maximum ovarian/uterine radiation dose increased. Radiation doses greater than 1,500 cGy were associated with a greater than fivefold increased risk of not having been pregnant, Dr. Green reported.

The investigators also looked at chemotherapy agents and found that alkylator and cyclophosphamide exposure was significantly associated with less likelihood of pregnancy in a dose-dependent manner.

In her discussion of these studies, Dr. Smita Bhatia of City of Hope National Medical Center in Duarte, Calif., said they highlight a critical need to increase awareness of the health problems faced by childhood cancer survivors—not only among the survivors themselves, but also among the primary physicians who provide most of their care.

One-third of childhood cancer survivors will have a life threatening complication 30 years out from diagnosis and treatment of their cancer, she said, citing a recent study (N. Engl. J. Med. 2006;355:1572-82).

“Primary cancer will continue to be treated with intense therapeutic exposure, and invariably will result in late effects. We need to focus on genetic predispositions and other factors which contribute toward these late effects, so that we can identify high-risk populations, and screen them appropriately to prevent these complications from happening and decrease the morbidity and mortality associated with late events,” she said.

Dr. Henderson, Dr. Green, and Dr. Bhatia all stated that they had no conflicts of interest to report.

CHICAGO — The treatment for pediatric cancers is becoming more successful, but at a price—increased incidences of new primary sarcomas and female infertility, according to two reports by the Childhood Cancer Survivor Study presented at the American Society of Clinical Oncology.

Exposure to radiation at doses over 10 Gy was the most important risk factor for the development of new sarcomas in childhood cancer survivors, said Dr. Tara O. Henderson of the University of Chicago.

Overall, radiation treatment was associated with an odds ratio of 4.7 for the development of a subsequent primary sarcoma. In patients who received more than 50 Gy, the odds ratio jumped to 31.6, Dr. Henderson reported.

The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study in 27 institutions in the United States and Canada. It includes 5-year survivors of leukemia, lymphoma, CNS cancer, bone cancer, Wilms' tumor, neuroblastoma, or soft-tissue sarcoma diagnosed between 1978 and 1986, with diagnoses at less than age 21 years.

Dr. Henderson and her associates found 127 confirmed sarcomas in a cohort of 14,372 survivors. Each case was matched by age, sex, and time since primary cancer diagnosis with four CCSS cohort members without subsequent sarcomas.

Radiation doses at the site of the subsequent sarcoma were estimated by medical physicists at the University of Texas M.D. Anderson Cancer Center, Houston, and chemotherapy information was obtained from patients' medical records.

Sarcomas occurred a median of 13 years (range 5-33 years) from the original cancer diagnosis.

Exposure to certain chemotherapy agents was also associated with risk for subsequent sarcomas. For anthracyclines, the odds ratio was 2.5; for bleomycin 4.6, and for alkylators 1.9.

In the second CCSS study, Dr. Daniel M. Green, of St. Jude Children's Research Hospital in Memphis, Tenn., reported that adult female survivors of childhood cancer were significantly less likely to have ever been pregnant, compared with their female siblings who did not have cancer.

Of the 5,149 survivors, 1,506 (29%) had ever achieved pregnancy, compared with 613 of the 1,441 siblings (43%) (relative risk, 0.81).

The risk of ever being pregnant decreased as the maximum ovarian/uterine radiation dose increased. Radiation doses greater than 1,500 cGy were associated with a greater than fivefold increased risk of not having been pregnant, Dr. Green reported.

The investigators also looked at chemotherapy agents and found that alkylator and cyclophosphamide exposure was significantly associated with less likelihood of pregnancy in a dose-dependent manner.

In her discussion of these studies, Dr. Smita Bhatia of City of Hope National Medical Center in Duarte, Calif., said they highlight a critical need to increase awareness of the health problems faced by childhood cancer survivors—not only among the survivors themselves, but also among the primary physicians who provide most of their care.

One-third of childhood cancer survivors will have a life threatening complication 30 years out from diagnosis and treatment of their cancer, she said, citing a recent study (N. Engl. J. Med. 2006;355:1572-82).

“Primary cancer will continue to be treated with intense therapeutic exposure, and invariably will result in late effects. We need to focus on genetic predispositions and other factors which contribute toward these late effects, so that we can identify high-risk populations, and screen them appropriately to prevent these complications from happening and decrease the morbidity and mortality associated with late events,” she said.

Dr. Henderson, Dr. Green, and Dr. Bhatia all stated that they had no conflicts of interest to report.

CHICAGO — Magnetic resonance imaging can detect cancer that is missed by mammography and physical examination in women aged 70 years or older, a retrospective single-institution study suggests.

The review of 159 elderly women with newly diagnosed breast cancer found MRI detected a contralateral cancer in 9 patients, even when mammography and palpation failed to do so, Dr. Johnny R. Bernard Jr. reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer risk increases with age, so that by the time a woman reaches age 70, she has a 1 in 15 chance of developing invasive breast cancer. Women with newly diagnosed breast cancer are also at high risk for having cancer in the contralateral breast. This combination of factors makes elderly women a high-risk cohort likely to benefit from enhanced screening with MRI, said Dr. Bernard, of the Mayo Clinic in Jacksonville, Fla.

The review included 159 women aged 70 or older (median age 75, range 70-91 years) at the time of their breast cancer diagnosis who had no evidence of cancer in the contralateral breast by mammogram or physical examination. All of the women had bilateral breast MRI between 2003 and 2007 at the Mayo Clinic's Jacksonville campus.

Mammographically occult contralateral abnormalities were noted in 65 of the women, and a biopsy was performed in 28 by Mayo Clinic pathologists. Nine of the 28 biopsies (32%) revealed pathologically confirmed carcinomas; 5 had invasive ductal carcinomas and 4 had ductal carcinomas in situ. All were node-negative stage 0-1 cancers. The other 18 biopsies were benign, for an overall prevalence of mammographically occult contralateral carcinoma of 6% for the study population as a whole, Dr. Bernard said.

MRI performed very well in this population, he added, with both sensitivity and negative predictive value of 100%. Specificity was 87%, and positive predictive value was 32%. “We recommend that older women should not be discriminated against with regard to breast MRI. At this time, we consider contralateral MRIs the standard of care at our institution,” he said.

In the question-and-answer period, Dr. Bernard was asked about the potential hazards of MRI screening in older women, such as overdiagnosis, unnecessarily aggressive treatment, and increased patient anxiety. He said these risks are well known, but that older women deserve the same considerations as younger women.

“We know from social security life tables that women who are aged 70 have a life expectancy of about 16 years; a woman of age 80 has a life expectancy of 10 years, age 85, it is 7.2 years,” he said. “If a woman has no significant comorbidities, or has minimal comorbidities, and if she has a life expectancy of at least 5 years, she is expected to benefit from screening mammography. We feel women will also benefit from screening MRI.”

He added that risks and benefits of treatment are always discussed beforehand. “We allow our patients to participate in our decision-making process,” he said.

Discussant Dr. Robyn L. Birdwell, of Harvard Medical School and Brigham & Women's Hospital in Boston, underscored Dr. Bernard's comments about offering older women the same screening options as younger women.

“Both patients and their physicians underestimate life expectancy in women,” she said. “In the healthy population of older women, 15 years is quite a bit of time to expect, and we need to be aware of this tendency to underestimate life expectancy.”

She predicted that MRI screening for breast cancer would be increasingly used in women who are recognizable as high risk, such as the elderly.

Neither Dr. Bernard nor Dr. Birdwell disclosed any conflicts of interest.

'At this time, we consider contralateral MRIs the standard of care at our institution.' DR. BERNARD

CHICAGO — Magnetic resonance imaging can detect cancer that is missed by mammography and physical examination in women aged 70 years or older, a retrospective single-institution study suggests.

The review of 159 elderly women with newly diagnosed breast cancer found MRI detected a contralateral cancer in 9 patients, even when mammography and palpation failed to do so, Dr. Johnny R. Bernard Jr. reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer risk increases with age, so that by the time a woman reaches age 70, she has a 1 in 15 chance of developing invasive breast cancer. Women with newly diagnosed breast cancer are also at high risk for having cancer in the contralateral breast. This combination of factors makes elderly women a high-risk cohort likely to benefit from enhanced screening with MRI, said Dr. Bernard, of the Mayo Clinic in Jacksonville, Fla.

The review included 159 women aged 70 or older (median age 75, range 70-91 years) at the time of their breast cancer diagnosis who had no evidence of cancer in the contralateral breast by mammogram or physical examination. All of the women had bilateral breast MRI between 2003 and 2007 at the Mayo Clinic's Jacksonville campus.

Mammographically occult contralateral abnormalities were noted in 65 of the women, and a biopsy was performed in 28 by Mayo Clinic pathologists. Nine of the 28 biopsies (32%) revealed pathologically confirmed carcinomas; 5 had invasive ductal carcinomas and 4 had ductal carcinomas in situ. All were node-negative stage 0-1 cancers. The other 18 biopsies were benign, for an overall prevalence of mammographically occult contralateral carcinoma of 6% for the study population as a whole, Dr. Bernard said.

MRI performed very well in this population, he added, with both sensitivity and negative predictive value of 100%. Specificity was 87%, and positive predictive value was 32%. “We recommend that older women should not be discriminated against with regard to breast MRI. At this time, we consider contralateral MRIs the standard of care at our institution,” he said.

In the question-and-answer period, Dr. Bernard was asked about the potential hazards of MRI screening in older women, such as overdiagnosis, unnecessarily aggressive treatment, and increased patient anxiety. He said these risks are well known, but that older women deserve the same considerations as younger women.

“We know from social security life tables that women who are aged 70 have a life expectancy of about 16 years; a woman of age 80 has a life expectancy of 10 years, age 85, it is 7.2 years,” he said. “If a woman has no significant comorbidities, or has minimal comorbidities, and if she has a life expectancy of at least 5 years, she is expected to benefit from screening mammography. We feel women will also benefit from screening MRI.”

He added that risks and benefits of treatment are always discussed beforehand. “We allow our patients to participate in our decision-making process,” he said.

Discussant Dr. Robyn L. Birdwell, of Harvard Medical School and Brigham & Women's Hospital in Boston, underscored Dr. Bernard's comments about offering older women the same screening options as younger women.

“Both patients and their physicians underestimate life expectancy in women,” she said. “In the healthy population of older women, 15 years is quite a bit of time to expect, and we need to be aware of this tendency to underestimate life expectancy.”

She predicted that MRI screening for breast cancer would be increasingly used in women who are recognizable as high risk, such as the elderly.

Neither Dr. Bernard nor Dr. Birdwell disclosed any conflicts of interest.

'At this time, we consider contralateral MRIs the standard of care at our institution.' DR. BERNARD

CHICAGO — Magnetic resonance imaging can detect cancer that is missed by mammography and physical examination in women aged 70 years or older, a retrospective single-institution study suggests.

The review of 159 elderly women with newly diagnosed breast cancer found MRI detected a contralateral cancer in 9 patients, even when mammography and palpation failed to do so, Dr. Johnny R. Bernard Jr. reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer risk increases with age, so that by the time a woman reaches age 70, she has a 1 in 15 chance of developing invasive breast cancer. Women with newly diagnosed breast cancer are also at high risk for having cancer in the contralateral breast. This combination of factors makes elderly women a high-risk cohort likely to benefit from enhanced screening with MRI, said Dr. Bernard, of the Mayo Clinic in Jacksonville, Fla.

The review included 159 women aged 70 or older (median age 75, range 70-91 years) at the time of their breast cancer diagnosis who had no evidence of cancer in the contralateral breast by mammogram or physical examination. All of the women had bilateral breast MRI between 2003 and 2007 at the Mayo Clinic's Jacksonville campus.

Mammographically occult contralateral abnormalities were noted in 65 of the women, and a biopsy was performed in 28 by Mayo Clinic pathologists. Nine of the 28 biopsies (32%) revealed pathologically confirmed carcinomas; 5 had invasive ductal carcinomas and 4 had ductal carcinomas in situ. All were node-negative stage 0-1 cancers. The other 18 biopsies were benign, for an overall prevalence of mammographically occult contralateral carcinoma of 6% for the study population as a whole, Dr. Bernard said.

MRI performed very well in this population, he added, with both sensitivity and negative predictive value of 100%. Specificity was 87%, and positive predictive value was 32%. “We recommend that older women should not be discriminated against with regard to breast MRI. At this time, we consider contralateral MRIs the standard of care at our institution,” he said.

In the question-and-answer period, Dr. Bernard was asked about the potential hazards of MRI screening in older women, such as overdiagnosis, unnecessarily aggressive treatment, and increased patient anxiety. He said these risks are well known, but that older women deserve the same considerations as younger women.

“We know from social security life tables that women who are aged 70 have a life expectancy of about 16 years; a woman of age 80 has a life expectancy of 10 years, age 85, it is 7.2 years,” he said. “If a woman has no significant comorbidities, or has minimal comorbidities, and if she has a life expectancy of at least 5 years, she is expected to benefit from screening mammography. We feel women will also benefit from screening MRI.”

He added that risks and benefits of treatment are always discussed beforehand. “We allow our patients to participate in our decision-making process,” he said.

Discussant Dr. Robyn L. Birdwell, of Harvard Medical School and Brigham & Women's Hospital in Boston, underscored Dr. Bernard's comments about offering older women the same screening options as younger women.

“Both patients and their physicians underestimate life expectancy in women,” she said. “In the healthy population of older women, 15 years is quite a bit of time to expect, and we need to be aware of this tendency to underestimate life expectancy.”

She predicted that MRI screening for breast cancer would be increasingly used in women who are recognizable as high risk, such as the elderly.

Neither Dr. Bernard nor Dr. Birdwell disclosed any conflicts of interest.

'At this time, we consider contralateral MRIs the standard of care at our institution.' DR. BERNARD

CHICAGO — Advanced prostate cancer is being diagnosed increasingly in younger men aged 60 years or less in the United States, despite the widespread availability of prostate-specific antigen testing, according to epidemiologic evidence spanning 15 years from the Surveillance, Epidemiology, and End Results database.

“That's the bad news,” Dr. Michael Carducci said at the annual meeting of the American Society of Clinical Oncology, where he presented the data in a poster. “The good news is that they are living longer than ever before.”

Dr. Carducci, professor of medicine at Johns Hopkins University, Baltimore, tempered the good news with the observation that improved survival leaves these men vulnerable to serious physical and psychological side effects from increasingly successful treatments. Additionally, the natural history of advanced prostate cancer results in a protracted disease course, making reductions in quality of life a major concern, he said in an interview.

The retrospective cohort study, sponsored by Amgen Inc., found the age-adjusted incidence rate of stage IV prostate cancer was 28/100,000 men in 1988 and steadily declined to 12/100,000 men in 2003, for an average decrease of 6.4% per year (P less than .0001).

The proportion of stage IV prostate cancer patients diagnosed at younger ages increased over the course of the study, which was divided into two time periods—1988–1992 and 1998–2003. In the earlier time period, 1% of men 50 years or younger were diagnosed with stage IV prostate cancer; in the later time period, that proportion jumped to 4.1% (P less than .0001). Similarly, for men aged 51–60 years, that proportion went from 9% in 1988–1992 to 20% in 1998–2003 (P less than .0001).

Also noteworthy was the improvement in 5-year survival. From 1988 to 1999, this rate jumped from 43% to 61% among all stage IV patients, but the improvement was particularly dramatic in younger patients. Among men less than age 50 years, the 5-year survival went from 37% in 1988–1992 to 65% in 1998–1999, and in the 51- to 60-year-old age group, 5-year survival increased from 53% to 74%.

Dr. Carducci disclosed that he is a consultant to Amgen.

CHICAGO — Advanced prostate cancer is being diagnosed increasingly in younger men aged 60 years or less in the United States, despite the widespread availability of prostate-specific antigen testing, according to epidemiologic evidence spanning 15 years from the Surveillance, Epidemiology, and End Results database.

“That's the bad news,” Dr. Michael Carducci said at the annual meeting of the American Society of Clinical Oncology, where he presented the data in a poster. “The good news is that they are living longer than ever before.”

Dr. Carducci, professor of medicine at Johns Hopkins University, Baltimore, tempered the good news with the observation that improved survival leaves these men vulnerable to serious physical and psychological side effects from increasingly successful treatments. Additionally, the natural history of advanced prostate cancer results in a protracted disease course, making reductions in quality of life a major concern, he said in an interview.

The retrospective cohort study, sponsored by Amgen Inc., found the age-adjusted incidence rate of stage IV prostate cancer was 28/100,000 men in 1988 and steadily declined to 12/100,000 men in 2003, for an average decrease of 6.4% per year (P less than .0001).

The proportion of stage IV prostate cancer patients diagnosed at younger ages increased over the course of the study, which was divided into two time periods—1988–1992 and 1998–2003. In the earlier time period, 1% of men 50 years or younger were diagnosed with stage IV prostate cancer; in the later time period, that proportion jumped to 4.1% (P less than .0001). Similarly, for men aged 51–60 years, that proportion went from 9% in 1988–1992 to 20% in 1998–2003 (P less than .0001).

Also noteworthy was the improvement in 5-year survival. From 1988 to 1999, this rate jumped from 43% to 61% among all stage IV patients, but the improvement was particularly dramatic in younger patients. Among men less than age 50 years, the 5-year survival went from 37% in 1988–1992 to 65% in 1998–1999, and in the 51- to 60-year-old age group, 5-year survival increased from 53% to 74%.

Dr. Carducci disclosed that he is a consultant to Amgen.

CHICAGO — Advanced prostate cancer is being diagnosed increasingly in younger men aged 60 years or less in the United States, despite the widespread availability of prostate-specific antigen testing, according to epidemiologic evidence spanning 15 years from the Surveillance, Epidemiology, and End Results database.

“That's the bad news,” Dr. Michael Carducci said at the annual meeting of the American Society of Clinical Oncology, where he presented the data in a poster. “The good news is that they are living longer than ever before.”

Dr. Carducci, professor of medicine at Johns Hopkins University, Baltimore, tempered the good news with the observation that improved survival leaves these men vulnerable to serious physical and psychological side effects from increasingly successful treatments. Additionally, the natural history of advanced prostate cancer results in a protracted disease course, making reductions in quality of life a major concern, he said in an interview.

The retrospective cohort study, sponsored by Amgen Inc., found the age-adjusted incidence rate of stage IV prostate cancer was 28/100,000 men in 1988 and steadily declined to 12/100,000 men in 2003, for an average decrease of 6.4% per year (P less than .0001).

The proportion of stage IV prostate cancer patients diagnosed at younger ages increased over the course of the study, which was divided into two time periods—1988–1992 and 1998–2003. In the earlier time period, 1% of men 50 years or younger were diagnosed with stage IV prostate cancer; in the later time period, that proportion jumped to 4.1% (P less than .0001). Similarly, for men aged 51–60 years, that proportion went from 9% in 1988–1992 to 20% in 1998–2003 (P less than .0001).

Also noteworthy was the improvement in 5-year survival. From 1988 to 1999, this rate jumped from 43% to 61% among all stage IV patients, but the improvement was particularly dramatic in younger patients. Among men less than age 50 years, the 5-year survival went from 37% in 1988–1992 to 65% in 1998–1999, and in the 51- to 60-year-old age group, 5-year survival increased from 53% to 74%.

Dr. Carducci disclosed that he is a consultant to Amgen.

CHICAGO — The widely used diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients taking metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%, P = .007), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston reported in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in patients without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy (P = .099).

Recent epidemiologic studies suggest that metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. The drug activates adenosine monophsphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in pre-clinical studies, said Dr. Jiralerspong.

To explore the possibility that metformin's antiproliferative effects might increase the efficacy of neoadjuvant chemotherapy in diabetic breast cancer patients, Dr. Jiralerspong and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early stage breast cancer.

Ninety-four percent of patients (2,374) did not have diabetes; 68 patients had diabetes and were treated with metformin, and 87 patients had diabetes but were not treated with metformin. The median age of the full study population was 49 years (range 21–87 years), most of the tumors were hormone receptor-positive, and 25% were HER2-positive. Baseline characteristics of patients with and without diabetes were similar, although the diabetic groups tended to be slightly older and more obese, Dr. Jiralerspong noted.

Metformin use was independently predictive of pCR (odds ratio 3.2, P = .023) after adjustment for diabetes, body mass index, age, stage, grade, estrogen receptor (ER)/progesterone receptor (PR) status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, however, in the nondiabetic cohort (86%), compared with 81% for the diabetic patients on metformin and 78% for the diabetic patients not on metformin (P = .02).

“This could just be due to short follow-up, and also there may be other factors at play. Diabetics probably are going to do worse in general, and we are starting to look at the causes of death now because it might have been noncancer causes of death that produced these results,” Dr. Jiralerspong said.

He emphasized that this retrospective analysis was hypothesis generating, but said that the results warrant prospective studies to more fully evaluate the potential of metformin as an antitumor agent.

Dr. Jiralerspong said he had no conflicts of interest to declare.

CHICAGO — The widely used diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients taking metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%, P = .007), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston reported in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in patients without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy (P = .099).

Recent epidemiologic studies suggest that metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. The drug activates adenosine monophsphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in pre-clinical studies, said Dr. Jiralerspong.

To explore the possibility that metformin's antiproliferative effects might increase the efficacy of neoadjuvant chemotherapy in diabetic breast cancer patients, Dr. Jiralerspong and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early stage breast cancer.

Ninety-four percent of patients (2,374) did not have diabetes; 68 patients had diabetes and were treated with metformin, and 87 patients had diabetes but were not treated with metformin. The median age of the full study population was 49 years (range 21–87 years), most of the tumors were hormone receptor-positive, and 25% were HER2-positive. Baseline characteristics of patients with and without diabetes were similar, although the diabetic groups tended to be slightly older and more obese, Dr. Jiralerspong noted.

Metformin use was independently predictive of pCR (odds ratio 3.2, P = .023) after adjustment for diabetes, body mass index, age, stage, grade, estrogen receptor (ER)/progesterone receptor (PR) status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, however, in the nondiabetic cohort (86%), compared with 81% for the diabetic patients on metformin and 78% for the diabetic patients not on metformin (P = .02).

“This could just be due to short follow-up, and also there may be other factors at play. Diabetics probably are going to do worse in general, and we are starting to look at the causes of death now because it might have been noncancer causes of death that produced these results,” Dr. Jiralerspong said.

He emphasized that this retrospective analysis was hypothesis generating, but said that the results warrant prospective studies to more fully evaluate the potential of metformin as an antitumor agent.

Dr. Jiralerspong said he had no conflicts of interest to declare.

CHICAGO — The widely used diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients taking metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%, P = .007), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston reported in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in patients without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy (P = .099).

Recent epidemiologic studies suggest that metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. The drug activates adenosine monophsphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in pre-clinical studies, said Dr. Jiralerspong.

To explore the possibility that metformin's antiproliferative effects might increase the efficacy of neoadjuvant chemotherapy in diabetic breast cancer patients, Dr. Jiralerspong and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early stage breast cancer.

Ninety-four percent of patients (2,374) did not have diabetes; 68 patients had diabetes and were treated with metformin, and 87 patients had diabetes but were not treated with metformin. The median age of the full study population was 49 years (range 21–87 years), most of the tumors were hormone receptor-positive, and 25% were HER2-positive. Baseline characteristics of patients with and without diabetes were similar, although the diabetic groups tended to be slightly older and more obese, Dr. Jiralerspong noted.

Metformin use was independently predictive of pCR (odds ratio 3.2, P = .023) after adjustment for diabetes, body mass index, age, stage, grade, estrogen receptor (ER)/progesterone receptor (PR) status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, however, in the nondiabetic cohort (86%), compared with 81% for the diabetic patients on metformin and 78% for the diabetic patients not on metformin (P = .02).

“This could just be due to short follow-up, and also there may be other factors at play. Diabetics probably are going to do worse in general, and we are starting to look at the causes of death now because it might have been noncancer causes of death that produced these results,” Dr. Jiralerspong said.

He emphasized that this retrospective analysis was hypothesis generating, but said that the results warrant prospective studies to more fully evaluate the potential of metformin as an antitumor agent.

Dr. Jiralerspong said he had no conflicts of interest to declare.

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D3 per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression also increased, but to a lesser extent (33%), reported Veronika Fedirko, a PhD candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months: 2,000 mg calcium a day (23 patients); 2,000 mg calcium plus 800 IU vitamin D a day (23); 800 IU vitamin D a day (23); or placebo (23).

Patients underwent a colorectal biopsy at study entry and another biopsy at the end of the study period. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months, Bax expression along the full lengths of the colorectal crypts rose by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium-plus-vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, said the researchers. They also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium-plus-vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with placebo. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas,” said the researchers.

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D3 per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression also increased, but to a lesser extent (33%), reported Veronika Fedirko, a PhD candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months: 2,000 mg calcium a day (23 patients); 2,000 mg calcium plus 800 IU vitamin D a day (23); 800 IU vitamin D a day (23); or placebo (23).

Patients underwent a colorectal biopsy at study entry and another biopsy at the end of the study period. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months, Bax expression along the full lengths of the colorectal crypts rose by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium-plus-vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, said the researchers. They also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium-plus-vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with placebo. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas,” said the researchers.

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D3 per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression also increased, but to a lesser extent (33%), reported Veronika Fedirko, a PhD candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months: 2,000 mg calcium a day (23 patients); 2,000 mg calcium plus 800 IU vitamin D a day (23); 800 IU vitamin D a day (23); or placebo (23).

Patients underwent a colorectal biopsy at study entry and another biopsy at the end of the study period. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months, Bax expression along the full lengths of the colorectal crypts rose by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium-plus-vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, said the researchers. They also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium-plus-vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with placebo. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas,” said the researchers.