Jennie Smith

The World Health Organization said June 3 that the number of cases of hemorrhagic diarrhea and hemolytic uremic syndrome due to infection with a dangerous and possibly novel Escherichia coli serotype continues to climb, mainly in Germany.

Since the outbreak began in early May, 1,823 cases of enterohemorrhagic E. coli, or EHEC, have been reported altogether. There have been 552 cases of hemolytic uremic syndrome, or HUS, a dangerous nephrologic complication, and 18 fatalities.

Courtesy Wikimedia Commons/Ksd5/Creative Commons License

Most of the morbidity and mortality – 1,733 total cases, 520 HUS cases, and 17 deaths – has occurred in Germany alone, WHO said in an epidemiologic update published June 3.

At a separate June 3 briefing, U.S. health officials sought to reassure Americans that there is no reason to believe that the EHEC virus will spread to the United States. 

The strain causing illness in Europe, STEC O104:H4, “is very rare,” said Dr. Chris Braden, director of Foodborne, Waterborne, and Environmental Diseases at the Centers for Disease Control and Prevention.

“The CDC is not aware of any confirmed cases of this infection ever reported in the United States," Dr. Braden said during a press briefing. "However, we have become aware of some similar strains that have been identified in other countries in the world in the past.”

There are currently four suspected cases of this infection in the United States, Dr. Braden said. Each suspected case has been identified in persons who traveled to Hamburg, Germany, in May 2011. “In the other countries outside of Germany in Europe and in the United States, the persons who became ill were exposed in Germany and became ill in their home countries after exposure,” he said. “We are continuing to monitor these cases closely. The risk of person-to-person transmission is low.”

The CDC is working with state health departments to learn more about these suspected cases and to obtain bacterial isolates “for further characterization.”

Dr. Braden noted that there are no confirmed cases of STEC infection among U.S. military personnel or their dependents at this time. However, two service members in Germany with diarrheal illness are being evaluated as suspect cases.

The CDC will provide updates on the situation at www.cdc.gov/ecoli.

The German case count jumped dramatically since the beginning of the week, with 50 new cases of HUS and 149 cases of EHEC reported to national health authorities since May 31; however, a public holiday June 2 may have depressed notifications, and officials at the Robert Koch Institute (RKI) in Berlin acknowledged that the true count may be higher.

The rare shiga toxin–producing strain of E. coli responsible for the outbreak has been variously reported as novel and previously isolated, though it is not known to be responsible for any prior outbreaks.

The Robert Koch Institute, Germany’s national epidemiologic agency, emphasized in a statement June 3 that the causative agent, the STEC O104:H4, was not entirely new, as has been reported, though it had never before been responsible for an outbreak.

The previous day, BGI-Shenzhen, a genomics institute based in Shenzhen, China, had claimed that its sequencing efforts, on samples received from European health agencies, had revealed the agent to be "an entirely new super-toxic E. coli strain."

The disease-causing strain, BGI said on its website, "shares 93% sequence similarity with the EAEC 55989 E. coli strain, which was isolated in the Central African Republic and known to cause serious diarrhea," but with new sequences that may be involved in the pathogenicity of hemorrhagic colitis and HUS. The serogroup, BGI said, "carries several antibiotic resistance genes, including resistance to aminoglycoside, macrolides and beta-lactam antibiotics."

Though cases have now been reported in 12 European countries and the United States, nearly all have occurred among people with recent travel to northern Germany or who received visitors from that region. As of June 2, a majority of patients were aged 20 years or older (88%) and female (71%), a pattern departing from typical E. coli outbreaks, according to a June 2 update by scientists at RKI (Euro Surveill. 2011;16(22):pii=19883).

RKI is now conducting seven studies on the outbreak, including case-control studies in heavily affected hospitals; investigation of human-to-human transmission and food purchases made, by analysis of receipts, within the setting of an outbreak site; cohort investigations of groups in which members developed symptoms after dinner in a restaurant; exploration of several events and festivities potentially related to cases; and collecting data from nephrologists treating HUS cases.

However, the institute appears no closer to identifying a source than it was a week ago.

The vehicle of the outbreak, previously believed to be imported cucumbers, has not been identified, but vegetables remain a suspected source after a preliminary epidemiologic study, completed May 25, found infected people had eaten more of these foods than had noninfected people. The European Center for Disease Prevention and Control, in its own update June 3, maintained that "contaminated food" was the likeliest source of infection.

While RKI continues to advise Germans not to eat raw tomatoes, cucumbers, or lettuce, especially in the northern states, all of the above remained on sale in German supermarkets June 3, albeit in many cases steeply discounted.

Despite the outbreak of STEC infections in Germany , David Elder, director of regional operations for the Food and Drug Administration, emphasized that produce in the United States “remains safe, and there is no reason for Americans to alter where they shop, what they buy, and where they eat. The U.S. food supply is not in jeopardy.”

As a safety precaution, however, Mr. Elder said that the FDA established import controls within 24 hours of the health advisory issuing in Germany. “The FDA has increased its surveillance of cucumbers, fresh tomatoes, and lettuce from Spain and from Germany,” Mr. Elder said. “When any of these products are presented for import into the United States, the FDA will sample and analyze them in our laboratories.”

Mr. Elder said that an estimated 15% of the food supply in the United States is imported, including about 50% of fresh fruits, 20% of fresh vegetables, and up to 80% of seafoods.

U.S. military bases in Germany have elected to eliminate fresh produce items altogether in their grocery stores and restaurants until the source of the outbreak is identified.

Doug Brunk, San Diego bureau, contributed to this story.

The World Health Organization said June 3 that the number of cases of hemorrhagic diarrhea and hemolytic uremic syndrome due to infection with a dangerous and possibly novel Escherichia coli serotype continues to climb, mainly in Germany.

Since the outbreak began in early May, 1,823 cases of enterohemorrhagic E. coli, or EHEC, have been reported altogether. There have been 552 cases of hemolytic uremic syndrome, or HUS, a dangerous nephrologic complication, and 18 fatalities.

Courtesy Wikimedia Commons/Ksd5/Creative Commons License

Most of the morbidity and mortality – 1,733 total cases, 520 HUS cases, and 17 deaths – has occurred in Germany alone, WHO said in an epidemiologic update published June 3.

At a separate June 3 briefing, U.S. health officials sought to reassure Americans that there is no reason to believe that the EHEC virus will spread to the United States. 

The strain causing illness in Europe, STEC O104:H4, “is very rare,” said Dr. Chris Braden, director of Foodborne, Waterborne, and Environmental Diseases at the Centers for Disease Control and Prevention.

“The CDC is not aware of any confirmed cases of this infection ever reported in the United States," Dr. Braden said during a press briefing. "However, we have become aware of some similar strains that have been identified in other countries in the world in the past.”

There are currently four suspected cases of this infection in the United States, Dr. Braden said. Each suspected case has been identified in persons who traveled to Hamburg, Germany, in May 2011. “In the other countries outside of Germany in Europe and in the United States, the persons who became ill were exposed in Germany and became ill in their home countries after exposure,” he said. “We are continuing to monitor these cases closely. The risk of person-to-person transmission is low.”

The CDC is working with state health departments to learn more about these suspected cases and to obtain bacterial isolates “for further characterization.”

Dr. Braden noted that there are no confirmed cases of STEC infection among U.S. military personnel or their dependents at this time. However, two service members in Germany with diarrheal illness are being evaluated as suspect cases.

The CDC will provide updates on the situation at www.cdc.gov/ecoli.

The German case count jumped dramatically since the beginning of the week, with 50 new cases of HUS and 149 cases of EHEC reported to national health authorities since May 31; however, a public holiday June 2 may have depressed notifications, and officials at the Robert Koch Institute (RKI) in Berlin acknowledged that the true count may be higher.

The rare shiga toxin–producing strain of E. coli responsible for the outbreak has been variously reported as novel and previously isolated, though it is not known to be responsible for any prior outbreaks.

The Robert Koch Institute, Germany’s national epidemiologic agency, emphasized in a statement June 3 that the causative agent, the STEC O104:H4, was not entirely new, as has been reported, though it had never before been responsible for an outbreak.

The previous day, BGI-Shenzhen, a genomics institute based in Shenzhen, China, had claimed that its sequencing efforts, on samples received from European health agencies, had revealed the agent to be "an entirely new super-toxic E. coli strain."

The disease-causing strain, BGI said on its website, "shares 93% sequence similarity with the EAEC 55989 E. coli strain, which was isolated in the Central African Republic and known to cause serious diarrhea," but with new sequences that may be involved in the pathogenicity of hemorrhagic colitis and HUS. The serogroup, BGI said, "carries several antibiotic resistance genes, including resistance to aminoglycoside, macrolides and beta-lactam antibiotics."

Though cases have now been reported in 12 European countries and the United States, nearly all have occurred among people with recent travel to northern Germany or who received visitors from that region. As of June 2, a majority of patients were aged 20 years or older (88%) and female (71%), a pattern departing from typical E. coli outbreaks, according to a June 2 update by scientists at RKI (Euro Surveill. 2011;16(22):pii=19883).

RKI is now conducting seven studies on the outbreak, including case-control studies in heavily affected hospitals; investigation of human-to-human transmission and food purchases made, by analysis of receipts, within the setting of an outbreak site; cohort investigations of groups in which members developed symptoms after dinner in a restaurant; exploration of several events and festivities potentially related to cases; and collecting data from nephrologists treating HUS cases.

However, the institute appears no closer to identifying a source than it was a week ago.

The vehicle of the outbreak, previously believed to be imported cucumbers, has not been identified, but vegetables remain a suspected source after a preliminary epidemiologic study, completed May 25, found infected people had eaten more of these foods than had noninfected people. The European Center for Disease Prevention and Control, in its own update June 3, maintained that "contaminated food" was the likeliest source of infection.

While RKI continues to advise Germans not to eat raw tomatoes, cucumbers, or lettuce, especially in the northern states, all of the above remained on sale in German supermarkets June 3, albeit in many cases steeply discounted.

Despite the outbreak of STEC infections in Germany , David Elder, director of regional operations for the Food and Drug Administration, emphasized that produce in the United States “remains safe, and there is no reason for Americans to alter where they shop, what they buy, and where they eat. The U.S. food supply is not in jeopardy.”

As a safety precaution, however, Mr. Elder said that the FDA established import controls within 24 hours of the health advisory issuing in Germany. “The FDA has increased its surveillance of cucumbers, fresh tomatoes, and lettuce from Spain and from Germany,” Mr. Elder said. “When any of these products are presented for import into the United States, the FDA will sample and analyze them in our laboratories.”

Mr. Elder said that an estimated 15% of the food supply in the United States is imported, including about 50% of fresh fruits, 20% of fresh vegetables, and up to 80% of seafoods.

U.S. military bases in Germany have elected to eliminate fresh produce items altogether in their grocery stores and restaurants until the source of the outbreak is identified.

Doug Brunk, San Diego bureau, contributed to this story.

The World Health Organization said June 3 that the number of cases of hemorrhagic diarrhea and hemolytic uremic syndrome due to infection with a dangerous and possibly novel Escherichia coli serotype continues to climb, mainly in Germany.

Since the outbreak began in early May, 1,823 cases of enterohemorrhagic E. coli, or EHEC, have been reported altogether. There have been 552 cases of hemolytic uremic syndrome, or HUS, a dangerous nephrologic complication, and 18 fatalities.

Courtesy Wikimedia Commons/Ksd5/Creative Commons License

Most of the morbidity and mortality – 1,733 total cases, 520 HUS cases, and 17 deaths – has occurred in Germany alone, WHO said in an epidemiologic update published June 3.

At a separate June 3 briefing, U.S. health officials sought to reassure Americans that there is no reason to believe that the EHEC virus will spread to the United States. 

The strain causing illness in Europe, STEC O104:H4, “is very rare,” said Dr. Chris Braden, director of Foodborne, Waterborne, and Environmental Diseases at the Centers for Disease Control and Prevention.

“The CDC is not aware of any confirmed cases of this infection ever reported in the United States," Dr. Braden said during a press briefing. "However, we have become aware of some similar strains that have been identified in other countries in the world in the past.”

There are currently four suspected cases of this infection in the United States, Dr. Braden said. Each suspected case has been identified in persons who traveled to Hamburg, Germany, in May 2011. “In the other countries outside of Germany in Europe and in the United States, the persons who became ill were exposed in Germany and became ill in their home countries after exposure,” he said. “We are continuing to monitor these cases closely. The risk of person-to-person transmission is low.”

The CDC is working with state health departments to learn more about these suspected cases and to obtain bacterial isolates “for further characterization.”

Dr. Braden noted that there are no confirmed cases of STEC infection among U.S. military personnel or their dependents at this time. However, two service members in Germany with diarrheal illness are being evaluated as suspect cases.

The CDC will provide updates on the situation at www.cdc.gov/ecoli.

The German case count jumped dramatically since the beginning of the week, with 50 new cases of HUS and 149 cases of EHEC reported to national health authorities since May 31; however, a public holiday June 2 may have depressed notifications, and officials at the Robert Koch Institute (RKI) in Berlin acknowledged that the true count may be higher.

The rare shiga toxin–producing strain of E. coli responsible for the outbreak has been variously reported as novel and previously isolated, though it is not known to be responsible for any prior outbreaks.

The Robert Koch Institute, Germany’s national epidemiologic agency, emphasized in a statement June 3 that the causative agent, the STEC O104:H4, was not entirely new, as has been reported, though it had never before been responsible for an outbreak.

The previous day, BGI-Shenzhen, a genomics institute based in Shenzhen, China, had claimed that its sequencing efforts, on samples received from European health agencies, had revealed the agent to be "an entirely new super-toxic E. coli strain."

The disease-causing strain, BGI said on its website, "shares 93% sequence similarity with the EAEC 55989 E. coli strain, which was isolated in the Central African Republic and known to cause serious diarrhea," but with new sequences that may be involved in the pathogenicity of hemorrhagic colitis and HUS. The serogroup, BGI said, "carries several antibiotic resistance genes, including resistance to aminoglycoside, macrolides and beta-lactam antibiotics."

Though cases have now been reported in 12 European countries and the United States, nearly all have occurred among people with recent travel to northern Germany or who received visitors from that region. As of June 2, a majority of patients were aged 20 years or older (88%) and female (71%), a pattern departing from typical E. coli outbreaks, according to a June 2 update by scientists at RKI (Euro Surveill. 2011;16(22):pii=19883).

RKI is now conducting seven studies on the outbreak, including case-control studies in heavily affected hospitals; investigation of human-to-human transmission and food purchases made, by analysis of receipts, within the setting of an outbreak site; cohort investigations of groups in which members developed symptoms after dinner in a restaurant; exploration of several events and festivities potentially related to cases; and collecting data from nephrologists treating HUS cases.

However, the institute appears no closer to identifying a source than it was a week ago.

The vehicle of the outbreak, previously believed to be imported cucumbers, has not been identified, but vegetables remain a suspected source after a preliminary epidemiologic study, completed May 25, found infected people had eaten more of these foods than had noninfected people. The European Center for Disease Prevention and Control, in its own update June 3, maintained that "contaminated food" was the likeliest source of infection.

While RKI continues to advise Germans not to eat raw tomatoes, cucumbers, or lettuce, especially in the northern states, all of the above remained on sale in German supermarkets June 3, albeit in many cases steeply discounted.

Despite the outbreak of STEC infections in Germany , David Elder, director of regional operations for the Food and Drug Administration, emphasized that produce in the United States “remains safe, and there is no reason for Americans to alter where they shop, what they buy, and where they eat. The U.S. food supply is not in jeopardy.”

As a safety precaution, however, Mr. Elder said that the FDA established import controls within 24 hours of the health advisory issuing in Germany. “The FDA has increased its surveillance of cucumbers, fresh tomatoes, and lettuce from Spain and from Germany,” Mr. Elder said. “When any of these products are presented for import into the United States, the FDA will sample and analyze them in our laboratories.”

Mr. Elder said that an estimated 15% of the food supply in the United States is imported, including about 50% of fresh fruits, 20% of fresh vegetables, and up to 80% of seafoods.

U.S. military bases in Germany have elected to eliminate fresh produce items altogether in their grocery stores and restaurants until the source of the outbreak is identified.

Doug Brunk, San Diego bureau, contributed to this story.

Major Finding: In men with type 2 diabetes, mortality was significantly higher in those with untreated low testosterone (20%) than in those with either normal testosterone (9%) or treated low testosterone (8.6%).

Data Source: 580 men with type 2 diabetes who had total testosterone evaluated during 2002-2004 and were followed for about 6 years.

Disclosures: Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels (Endocr. Abstracts 2011;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that although a prospective, long-term study was still needed, the mortality difference shown in this retrospective study was “quite dramatic.” The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A_1c, preexisting cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Major Finding: In men with type 2 diabetes, mortality was significantly higher in those with untreated low testosterone (20%) than in those with either normal testosterone (9%) or treated low testosterone (8.6%).

Data Source: 580 men with type 2 diabetes who had total testosterone evaluated during 2002-2004 and were followed for about 6 years.

Disclosures: Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels (Endocr. Abstracts 2011;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that although a prospective, long-term study was still needed, the mortality difference shown in this retrospective study was “quite dramatic.” The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A_1c, preexisting cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Major Finding: In men with type 2 diabetes, mortality was significantly higher in those with untreated low testosterone (20%) than in those with either normal testosterone (9%) or treated low testosterone (8.6%).

Data Source: 580 men with type 2 diabetes who had total testosterone evaluated during 2002-2004 and were followed for about 6 years.

Disclosures: Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels (Endocr. Abstracts 2011;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that although a prospective, long-term study was still needed, the mortality difference shown in this retrospective study was “quite dramatic.” The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A_1c, preexisting cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15–35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the society's meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15–35 years.

“An increase in breast cancer risk associated with cigarette smoking had not been established until recently,” Dr. Land said at a press conference announcing the findings, and noted that her group's study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that “healthy lifestyle choices provide women a way to reduce their risk of these four major cancers,” Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

They also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk. The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO's president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land's study highlighted “the incredible importance of lifestyle factors,” and offered a reminder of the need to “think less about drugs and a great deal about whether we can prevent cancer.”

The study was funded by the National Cancer Institute. One of Dr. Land's coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15–35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the society's meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15–35 years.

“An increase in breast cancer risk associated with cigarette smoking had not been established until recently,” Dr. Land said at a press conference announcing the findings, and noted that her group's study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that “healthy lifestyle choices provide women a way to reduce their risk of these four major cancers,” Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

They also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk. The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO's president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land's study highlighted “the incredible importance of lifestyle factors,” and offered a reminder of the need to “think less about drugs and a great deal about whether we can prevent cancer.”

The study was funded by the National Cancer Institute. One of Dr. Land's coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Women who smoke for 35 years or more have a 59% higher risk of developing breast cancer, compared with those who never smoked, while those who smoked for 15–35 years had a 34% higher risk, according to data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, a 5-year randomized placebo-controlled trial of tamoxifen in 13,388 healthy women at high risk of breast cancer because of family history or other factors. The data also show that smoking cigarettes is especially dangerous for this group of women.

The study, led by Stephanie Land, Ph.D., of the University of Pittsburgh also looked at the incidence of invasive endometrial, lung, and colon cancers among its subjects, who were followed a median of 8.7 years. The investigators also looked at the effect of self-reported alcohol use and exercise habits on the risk of all four types of cancer.

In an abstract released in advance of the society's meeting in Chicago, Dr. Land and her colleagues reported that colon cancer incidence was also four times higher among women who reported having smoked more than 35 years than for never smokers, and 7% higher for women who smoked for 15–35 years.

“An increase in breast cancer risk associated with cigarette smoking had not been established until recently,” Dr. Land said at a press conference announcing the findings, and noted that her group's study reported larger effects than had previously been seen.

While the findings show that smoking is even more dangerous for women at known risk of breast cancer, the good news is that “healthy lifestyle choices provide women a way to reduce their risk of these four major cancers,” Dr. Land said.

Not surprisingly, longtime smokers saw a significantly higher risk of lung cancer in the study. Women who smoked a pack of cigarettes per day for more than 35 years had a risk 30 times higher than did women who never smoked. Women who smoked less than one pack per day for more than 35 years had a 13-fold increase in lung cancer risk.

They also found a significant association between low levels of physical activity and a 72% increased risk of endometrial cancer, which they hypothesized might be related to obesity, a known risk factor for endometrial cancer.

Alcohol consumption, however, was not associated with increased cancer risk, a finding that differs from previous studies. Moderate alcohol consumption of up to one drink a day was associated with a 65% decreased risk of colon cancer, compared with those women who did not drink. More than one drink per day was not associated with increased risk. The investigators said several factors might have been different in this study from past studies, particularly that it enrolled fewer heavy drinkers (13.3% of subjects reported that they drank one or more drinks per day), compared with other studies.

In a press conference announcing these and other findings, Dr. George W. Sledge Jr., ASCO's president and the Ballve-Lantero Professor of Oncology at Indiana University, Indianapolis, said Dr. Land's study highlighted “the incredible importance of lifestyle factors,” and offered a reminder of the need to “think less about drugs and a great deal about whether we can prevent cancer.”

The study was funded by the National Cancer Institute. One of Dr. Land's coauthors, Dr. Donald Lawrence Wickerham, disclosed having consultant or advisory roles with Lilly and honoraria from AstraZeneca.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients.

The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio, 5.0; 95% confidence interval, 1.3–19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7–15.2), labor induction (OR, 2.3; 95% CI, 1.2–4.3), c-section (OR, 2.5; 95% CI, 1.4–4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4–36.6).

The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother's age, highest maternal education, parity, body mass index of 30 kg/m

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 [doi:10.1111/j.1471-0528.2011. 03004.x]).

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is “growing use of AEDs for pain and psychiatric conditions.”

One limitation of the study, Dr. Borthen and her colleagues wrote in their analysis, was a lack of data on seizure type and severity.

The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients.

The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio, 5.0; 95% confidence interval, 1.3–19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7–15.2), labor induction (OR, 2.3; 95% CI, 1.2–4.3), c-section (OR, 2.5; 95% CI, 1.4–4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4–36.6).

The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother's age, highest maternal education, parity, body mass index of 30 kg/m

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 [doi:10.1111/j.1471-0528.2011. 03004.x]).

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is “growing use of AEDs for pain and psychiatric conditions.”

One limitation of the study, Dr. Borthen and her colleagues wrote in their analysis, was a lack of data on seizure type and severity.

The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients.

The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio, 5.0; 95% confidence interval, 1.3–19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7–15.2), labor induction (OR, 2.3; 95% CI, 1.2–4.3), c-section (OR, 2.5; 95% CI, 1.4–4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4–36.6).

The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother's age, highest maternal education, parity, body mass index of 30 kg/m

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 [doi:10.1111/j.1471-0528.2011. 03004.x]).

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is “growing use of AEDs for pain and psychiatric conditions.”

One limitation of the study, Dr. Borthen and her colleagues wrote in their analysis, was a lack of data on seizure type and severity.

The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Beta-blockers – safe and inexpensive drugs used for 4 decades in the management of cardiovascular disease – have shown surprising promise in inhibiting breast cancer progression and metastasis.

Two retrospective observational studies, published May 31 in Journal of Clinical Oncology, offer the latest evidence that the drugs, which have a role in neuroendocrine signaling pathways, lower the risk of recurrence, metastasis, and cancer-specific mortality.

In an editorial comment (doi:10.1200/JCO.2011.35.8820) accompanying the articles, Dr. Patricia A. Ganz and Steven W. Cole, Ph.D., both of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, wrote that the findings raised "the intriguing possibility" that these and other agents targeted to other diseases might provide "previously unappreciated opportunities for therapeutic control of disease progression, metastasis, and disease recurrence."

Because of this, they argued, future clinical treatment trials should "endeavor to collect prospective data on relevant medication exposures, weight and weight gain, comorbid conditions, and behaviors that have the potential to influence the microenvironment of the tumor, as these may be potent mediators of prognosis and survival, and may or may not be effectively accounted for in randomization."

In both studies, women with breast cancer prescribed beta-blockers for hypertension and other cardiovascular conditions were compared with women not taking the drugs.

For the first study (doi:10.1200/JCO.2010.33.5422), Thomas I. Barron, Ph.D., of Trinity College Dublin and his colleagues used linked data from an Irish national tumor registry and a pharmacy database to set up a case-control comparison of women prescribed the beta-blockers propranolol (n = 70) or atenolol (n = 525) in the year before and after their breast cancer diagnoses. These women were matched 1:2 to 4,738 women not prescribed beta-blockers, with matching inclusive of age, socioeconomic status, tumor grade and stage, and comorbidities.

After a median follow-up period of 3.5 years for the propranolol group and controls and slightly less than 3 years for the atenolol group and controls, the investigators found significant reductions in tumor size and nodal or metastatic distribution for the propranolol users, but not for the atenolol users. The cumulative probability of breast cancer–specific mortality was significantly lower among propranolol users (HR, 0.19). Propranolol users were also significantly less likely to present with a T4 (OR, 0.24) or N2/N3/M1 (OR, 0.20) tumor compared with matched controls. However, the atenolol group saw neither a significant reduction in breast-cancer specific mortality nor a difference in T4 or N2/N3/M1 tumor incidence from the matched controls.

In the second study (doi:10.1200/JCO.2010.33.4441), Dr. Amal Melhem-Bertrandt of the M.D. Anderson Cancer Center at the University of Texas, Houston, and colleagues identified 1,413 patients treated for breast cancer in a 12-year period, comparing those with (n = 102) and without (n = 1,311) concurrent beta-blocker exposure for a pathologic complete response, relapse-free survival, and overall survival. Mean follow-up was 55 months in the beta-blocker group and 63 months in the nonuser group.

The investigators saw no difference in pathologic response for those taking beta-blockers; however, after adjustment for variables including age, race, and tumor grade, women on beta-blockers showed significantly greater relapse-free survival (HR, 0.52; P = .015) and a trend toward greater overall survival that did not reach statistical significance (HR, 0.64; P = .09).

In a triple-negative subgroup (n = 377), the investigators found significant effects for beta-blocker use on relapse-free (HR, 0.30; P = .03) but not overall survival (HR, 0.35; P = .05) after adjustment.

In their editorial, Dr. Ganz and Dr. Cole noted that the findings from the second study, in which most of the beta-blockers were the beta-1–selective agents metoprolol (42% of patients) followed by atenolol (37%), would seem to contradict Dr. Barron and his colleagues’ findings, in which only propranolol, which inhibits both beta 1 and beta 2, had a significant effect. However, they wrote, "Neither metoprolol or atenolol is totally beta-1 specific; both partially inhibit beta-2–adrenergic receptors as well."

The editorialists noted that the new findings build on recent animal work indicating that beta-adrenergic receptors affect breast tumor growth and metastasis, and also on a 2010 U.K. retrospective study (n = 466) that was the first to look at a variety of antihypertensive agents in women with breast cancer. It found that women treated simultaneously with beta-blockers had a 57% reduced risk of metastasis compared with breast cancer patients receiving either other types of antihypertensive drugs or no antihypertensive drugs. Women on beta-blockers also saw 71% less cancer-specific mortality after 10 years (Oncotarget 2010; 1: 628-38).

"Beta-adrenergic signaling appears to have little effect on the biologic processes involved in breast cancer initiation, but more strongly affects the biologic processes involved in the subsequent progression and metastasis of incipient tumors. Given these results from the laboratory, and the clinical results from three recent retrospective reports suggesting the potential to limit recurrence of incident tumors, perhaps it is time to consider proof-of-concept trials testing the value of [beta-blockers] in the setting of breast cancer," Dr. Ganz and Dr. Cole wrote.

Dr. Barron and his colleagues declared that they had no financial disclosures relevant to their study, which was funded by the Irish government. Dr. Melhem-Bertrandt and colleagues said they had no financial disclosures relevant to their study, which was supported by a grant from the National Institutes of Health. Dr. Ganz and Dr. Cole, who were supported by the Breast Cancer Research Foundation, the Jonsson Comprehensive Cancer Center Foundation, Susan G. Komen for the Cure, and the National Cancer Institute, also declared that they had no relevant financial disclosures.

Widespread elective abortion of female fetuses – particularly among families with girl children already – is the likeliest reason for a marked gender imbalance among Indian children in recent decades, researchers have learned.

Currently, the sex ratio in children aged 6 years and younger in India is 915 girls to 1,000 boys, the lowest ever recorded in India. The normal expected ratio would be between 950 and 975 girls per 1,000 boys.

The new study, published online May 24 in the Lancet, was the first to identify as a likely culprit the selective abortion of second-order girls, using data from national birth cohorts and censuses (Lancet 2011 May 24 [doi:10.1016/S0140- 6736(11)60649-1]).

For their research, Dr. Prabhat Jha of the Dalla Lana School of Public Health at the University of Toronto, along with his colleagues in India, analyzed sex ratios by birth order in surveys of 250,000 births in 1990-2005. They estimated totals of selective abortion of girls by assessing records of children through 6 years of age in the 1991, 2001, and 2011 censuses.

In 1990, the researchers found, there were 906 girls born for every 1,000 boys in India among all second-order births; in 2005, female second-order births had dropped to 836 for every 1,000 males, representing an annual decline of 0.52%. While sex ratios for births after a firstborn girl fell sharply in this period, sex ratios for births after a firstborn boy did not change – suggesting that families were aborting to ensure themselves at least one son.

The trend was seen in a majority of states in India and shown to be most pronounced among both higher-income and more-educated families, suggesting that India’s recent increases in literacy and per-person income might be contributing to increased selective abortion of second-order girls.

Selective abortion has been prohibited by Indian national law since 1996, Dr. Jha and his colleagues wrote in their analysis, yet few practitioners have been convicted for it, and it appears to be practiced in all states. While preference for sons is widespread among all social classes in India, wealthier people have more access to ultrasound and abortion services, including those offered illegally for sex selection.

Dr. Jha and his colleagues calculated the number of selective abortions by adjusting for excess mortality rates in girls, with each 1% decline in child sex ratio between birth and age 6 years representing between 1.2 and 3.6 million more selective abortions of girls. They estimated that selective abortions of girls rose from fewer than 2 million in the 1980s, to between 1.2 and 4.1 million in the 1990s, to between 3.1 and 6 million in 2000-2010.

The estimates of the actual numbers of selective abortions, Dr. Jha and his colleagues wrote, "are, by necessity, crude." They also noted as a potential weakness of their study that "the exact contribution of selective abortion of girls to the measured sex imbalance at ages 0-6 years in the censuses" was dependent on child mortality, which has tended historically in India to be heavier among girls, presumably because of resource allocation favoring boys. Also, not all births in India are recorded, and the family surveys used by Dr. Jha and his colleagues rely on a mother’s recall of her birth history.

Although "unmeasured biological factors, such as infections, might reduce or increase overall sex ratios at birth, they are unlikely to be conditional on birth order," Dr. Jha and his colleagues wrote.

Although Dr. Jha and his colleagues noted that the rate of increase in selective abortions of girls seems to have slowed, from 260% between 1991 and 2001 to 170% in the last decade. Still, they wrote in their analysis, "selective abortions of first-order girls might increase if fertility drops further, particularly in urban areas."

In an editorial accompanying Dr. Jha and his colleagues’ findings, Dr. S.V. Subramanian, Ph.D., of the Harvard University School of Public Health, Boston, and Daniel J. Corsi. Ph.D., of McMaster University, Hamilton, Ont., wrote that they found the decline in sex ratios "counterintuitive, in view of India’s progress in recent decades in improving the levels of female literacy and increases in income per person" (Lancet 2011 May 24 [doi:10.1016/S0140-6736(11)60709-5]).

With the sex ratio of children through 6 years in India at 915 girls for 1000 boys— "the lowest ratio recorded since data became available in 1961," Dr. Subramanian and Dr. Corsi wrote, the prospects for normalization appeared "grim."

The findings, they wrote, show that socioeconomic development has not offset the "dominance of the son-preference norm" in India. "The overall problem of sex imbalance seems to arise throughout India, including in Kerala, which has often been characterized as a model state for social development and gender equality."

Also, Dr. Subramanian and Dr. Corsi noted, the findings show that India’s Pre-Natal Diagnostic Techniques Act, the 1996 law making it illegal to use ultrasound for the purposes of sex-selective abortion, is not working. "The pervasive nature of the low sex ratio at birth suggests that this is not a consequence of a minority of errant physicians in a few states," they wrote.

Though Dr. Subramanian and Dr. Corsi argued that the medical community should take actions against errant physicians, they did not condemn the practice of sex-selective abortion altogether. Instead, they concluded with a provocative question to policy makers. If no male biases are noticeable for the first born, as is the case in India, "Should medical technology and services be allowed to play a part in letting a family plan their desired composition, especially when there is an active public policy effort to voluntarily limit family size to replacement level?"

Dr. Jha and his colleagues study was funded by the U.S. National Institutes of Health, the Canadian Institute of Health Research, the International Development Research Center, and the Li Ka Shing Knowledge Institute. Dr. Jha and his colleagues declared no conflicts of interest. Dr. Subramanian and Dr. Corsi also declared that they had no conflicts of interest.

Widespread elective abortion of female fetuses – particularly among families with girl children already – is the likeliest reason for a marked gender imbalance among Indian children in recent decades, researchers have learned.

Currently, the sex ratio in children aged 6 years and younger in India is 915 girls to 1,000 boys, the lowest ever recorded in India. The normal expected ratio would be between 950 and 975 girls per 1,000 boys.

The new study, published online May 24 in the Lancet, was the first to identify as a likely culprit the selective abortion of second-order girls, using data from national birth cohorts and censuses (Lancet 2011 May 24 [doi:10.1016/S0140- 6736(11)60649-1]).

For their research, Dr. Prabhat Jha of the Dalla Lana School of Public Health at the University of Toronto, along with his colleagues in India, analyzed sex ratios by birth order in surveys of 250,000 births in 1990-2005. They estimated totals of selective abortion of girls by assessing records of children through 6 years of age in the 1991, 2001, and 2011 censuses.

In 1990, the researchers found, there were 906 girls born for every 1,000 boys in India among all second-order births; in 2005, female second-order births had dropped to 836 for every 1,000 males, representing an annual decline of 0.52%. While sex ratios for births after a firstborn girl fell sharply in this period, sex ratios for births after a firstborn boy did not change – suggesting that families were aborting to ensure themselves at least one son.

The trend was seen in a majority of states in India and shown to be most pronounced among both higher-income and more-educated families, suggesting that India’s recent increases in literacy and per-person income might be contributing to increased selective abortion of second-order girls.

Selective abortion has been prohibited by Indian national law since 1996, Dr. Jha and his colleagues wrote in their analysis, yet few practitioners have been convicted for it, and it appears to be practiced in all states. While preference for sons is widespread among all social classes in India, wealthier people have more access to ultrasound and abortion services, including those offered illegally for sex selection.

Dr. Jha and his colleagues calculated the number of selective abortions by adjusting for excess mortality rates in girls, with each 1% decline in child sex ratio between birth and age 6 years representing between 1.2 and 3.6 million more selective abortions of girls. They estimated that selective abortions of girls rose from fewer than 2 million in the 1980s, to between 1.2 and 4.1 million in the 1990s, to between 3.1 and 6 million in 2000-2010.

The estimates of the actual numbers of selective abortions, Dr. Jha and his colleagues wrote, "are, by necessity, crude." They also noted as a potential weakness of their study that "the exact contribution of selective abortion of girls to the measured sex imbalance at ages 0-6 years in the censuses" was dependent on child mortality, which has tended historically in India to be heavier among girls, presumably because of resource allocation favoring boys. Also, not all births in India are recorded, and the family surveys used by Dr. Jha and his colleagues rely on a mother’s recall of her birth history.

Although "unmeasured biological factors, such as infections, might reduce or increase overall sex ratios at birth, they are unlikely to be conditional on birth order," Dr. Jha and his colleagues wrote.

Although Dr. Jha and his colleagues noted that the rate of increase in selective abortions of girls seems to have slowed, from 260% between 1991 and 2001 to 170% in the last decade. Still, they wrote in their analysis, "selective abortions of first-order girls might increase if fertility drops further, particularly in urban areas."

In an editorial accompanying Dr. Jha and his colleagues’ findings, Dr. S.V. Subramanian, Ph.D., of the Harvard University School of Public Health, Boston, and Daniel J. Corsi. Ph.D., of McMaster University, Hamilton, Ont., wrote that they found the decline in sex ratios "counterintuitive, in view of India’s progress in recent decades in improving the levels of female literacy and increases in income per person" (Lancet 2011 May 24 [doi:10.1016/S0140-6736(11)60709-5]).

With the sex ratio of children through 6 years in India at 915 girls for 1000 boys— "the lowest ratio recorded since data became available in 1961," Dr. Subramanian and Dr. Corsi wrote, the prospects for normalization appeared "grim."

The findings, they wrote, show that socioeconomic development has not offset the "dominance of the son-preference norm" in India. "The overall problem of sex imbalance seems to arise throughout India, including in Kerala, which has often been characterized as a model state for social development and gender equality."

Also, Dr. Subramanian and Dr. Corsi noted, the findings show that India’s Pre-Natal Diagnostic Techniques Act, the 1996 law making it illegal to use ultrasound for the purposes of sex-selective abortion, is not working. "The pervasive nature of the low sex ratio at birth suggests that this is not a consequence of a minority of errant physicians in a few states," they wrote.

Though Dr. Subramanian and Dr. Corsi argued that the medical community should take actions against errant physicians, they did not condemn the practice of sex-selective abortion altogether. Instead, they concluded with a provocative question to policy makers. If no male biases are noticeable for the first born, as is the case in India, "Should medical technology and services be allowed to play a part in letting a family plan their desired composition, especially when there is an active public policy effort to voluntarily limit family size to replacement level?"

Dr. Jha and his colleagues study was funded by the U.S. National Institutes of Health, the Canadian Institute of Health Research, the International Development Research Center, and the Li Ka Shing Knowledge Institute. Dr. Jha and his colleagues declared no conflicts of interest. Dr. Subramanian and Dr. Corsi also declared that they had no conflicts of interest.

Widespread elective abortion of female fetuses – particularly among families with girl children already – is the likeliest reason for a marked gender imbalance among Indian children in recent decades, researchers have learned.

Currently, the sex ratio in children aged 6 years and younger in India is 915 girls to 1,000 boys, the lowest ever recorded in India. The normal expected ratio would be between 950 and 975 girls per 1,000 boys.

The new study, published online May 24 in the Lancet, was the first to identify as a likely culprit the selective abortion of second-order girls, using data from national birth cohorts and censuses (Lancet 2011 May 24 [doi:10.1016/S0140- 6736(11)60649-1]).

For their research, Dr. Prabhat Jha of the Dalla Lana School of Public Health at the University of Toronto, along with his colleagues in India, analyzed sex ratios by birth order in surveys of 250,000 births in 1990-2005. They estimated totals of selective abortion of girls by assessing records of children through 6 years of age in the 1991, 2001, and 2011 censuses.

In 1990, the researchers found, there were 906 girls born for every 1,000 boys in India among all second-order births; in 2005, female second-order births had dropped to 836 for every 1,000 males, representing an annual decline of 0.52%. While sex ratios for births after a firstborn girl fell sharply in this period, sex ratios for births after a firstborn boy did not change – suggesting that families were aborting to ensure themselves at least one son.

The trend was seen in a majority of states in India and shown to be most pronounced among both higher-income and more-educated families, suggesting that India’s recent increases in literacy and per-person income might be contributing to increased selective abortion of second-order girls.

Selective abortion has been prohibited by Indian national law since 1996, Dr. Jha and his colleagues wrote in their analysis, yet few practitioners have been convicted for it, and it appears to be practiced in all states. While preference for sons is widespread among all social classes in India, wealthier people have more access to ultrasound and abortion services, including those offered illegally for sex selection.

Dr. Jha and his colleagues calculated the number of selective abortions by adjusting for excess mortality rates in girls, with each 1% decline in child sex ratio between birth and age 6 years representing between 1.2 and 3.6 million more selective abortions of girls. They estimated that selective abortions of girls rose from fewer than 2 million in the 1980s, to between 1.2 and 4.1 million in the 1990s, to between 3.1 and 6 million in 2000-2010.

The estimates of the actual numbers of selective abortions, Dr. Jha and his colleagues wrote, "are, by necessity, crude." They also noted as a potential weakness of their study that "the exact contribution of selective abortion of girls to the measured sex imbalance at ages 0-6 years in the censuses" was dependent on child mortality, which has tended historically in India to be heavier among girls, presumably because of resource allocation favoring boys. Also, not all births in India are recorded, and the family surveys used by Dr. Jha and his colleagues rely on a mother’s recall of her birth history.

Although "unmeasured biological factors, such as infections, might reduce or increase overall sex ratios at birth, they are unlikely to be conditional on birth order," Dr. Jha and his colleagues wrote.

Although Dr. Jha and his colleagues noted that the rate of increase in selective abortions of girls seems to have slowed, from 260% between 1991 and 2001 to 170% in the last decade. Still, they wrote in their analysis, "selective abortions of first-order girls might increase if fertility drops further, particularly in urban areas."

In an editorial accompanying Dr. Jha and his colleagues’ findings, Dr. S.V. Subramanian, Ph.D., of the Harvard University School of Public Health, Boston, and Daniel J. Corsi. Ph.D., of McMaster University, Hamilton, Ont., wrote that they found the decline in sex ratios "counterintuitive, in view of India’s progress in recent decades in improving the levels of female literacy and increases in income per person" (Lancet 2011 May 24 [doi:10.1016/S0140-6736(11)60709-5]).

With the sex ratio of children through 6 years in India at 915 girls for 1000 boys— "the lowest ratio recorded since data became available in 1961," Dr. Subramanian and Dr. Corsi wrote, the prospects for normalization appeared "grim."

The findings, they wrote, show that socioeconomic development has not offset the "dominance of the son-preference norm" in India. "The overall problem of sex imbalance seems to arise throughout India, including in Kerala, which has often been characterized as a model state for social development and gender equality."

Also, Dr. Subramanian and Dr. Corsi noted, the findings show that India’s Pre-Natal Diagnostic Techniques Act, the 1996 law making it illegal to use ultrasound for the purposes of sex-selective abortion, is not working. "The pervasive nature of the low sex ratio at birth suggests that this is not a consequence of a minority of errant physicians in a few states," they wrote.

Though Dr. Subramanian and Dr. Corsi argued that the medical community should take actions against errant physicians, they did not condemn the practice of sex-selective abortion altogether. Instead, they concluded with a provocative question to policy makers. If no male biases are noticeable for the first born, as is the case in India, "Should medical technology and services be allowed to play a part in letting a family plan their desired composition, especially when there is an active public policy effort to voluntarily limit family size to replacement level?"

Dr. Jha and his colleagues study was funded by the U.S. National Institutes of Health, the Canadian Institute of Health Research, the International Development Research Center, and the Li Ka Shing Knowledge Institute. Dr. Jha and his colleagues declared no conflicts of interest. Dr. Subramanian and Dr. Corsi also declared that they had no conflicts of interest.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.

Researchers have identified a genetic biomarker that can predict a patient’s likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology’s annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis*, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues’ data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

* The name of the institution where Dr. Schneider is affiliated has been corrected.