Jane Salodof MacNeil

SAN FRANCISCO — The live attenuated influenza vaccine known as FluMist is as safe as an inactivated virus vaccine for children who are infected by the human immunodeficiency virus and have CD4 percentages of 15% or greater, according to the findings of a randomized, controlled trial.

Investigators recorded similar toxicity profiles for FluMist and the trivalent inactivated virus (TIV) vaccine that is standard for this population, Dr. Sharon Nachman reported at the annual meeting of the Pediatric Academic Societies.

Prolonged shedding, a major concern, was not observed in either arm of the phase I-II trial, according to Dr. Nachman, chief of pediatric infectious diseases, department of pediatrics, State University of New York at Stony Brook.

“There were no unexpected toxicities or adverse events associated with administration of LAIV [live attenuated influenza virus] or TIV in HIV-positive children in this study,” she said, summarizing 6 months of follow-up on behalf of the Pediatric AIDS Clinical Trials Group.

The investigators randomized 243 HIV-positive children from 5 to 18 years of age at the start of the 2004–2005 flu season: 122 to LAIV and 121 to TIV.

The LAIV arm of the study received the FluMist formulation that is currently approved for healthy children and adults from the ages of 5 to 49 years. The vaccine is delivered intranasally, whereas TIV must be injected.

Entry criteria included a current viral load below 60,000 copies per milliliter. All participants had at least 16 weeks of stable antiretroviral therapy with three different antiretroviral agents from at least two therapeutic classes.

All of the children had been vaccinated with TIV in at least one of the two previous years as well.

“Ethnicity looks exactly like [the] demographic of perinatally infected children across the United States,” Dr. Nachman said.

She described the study arms as evenly matched with respect to mean age (11.4–11.9 years), CD4 percentage (33%–34%), and viral load (2.9 copies/mL in both groups).

Vaccine administration did not lead to clinically significant changes in CD4 count or viral load during the study. Nor were changes in antiretroviral therapy made necessary by vaccination.

Investigators detected influenza shedding in 31 of 115 LAIV recipients (27%) 3 days after they received the vaccine.

By day 28 only 1 of 119 subjects (0.9%) was shedding virus, and the results of a follow-up culture done on day 56 were negative.

During the first 28 days, eight children in the LAIV arm had nine events that may have been related to FluMist administration: fever (one), malaise (one), conjunctivitis (two), acute otitis media (one), sinusitis (one), pharyngitis (one), and lower respiratory tract illness (one). One child was hospitalized and recovered with antibiotic therapy, Dr. Nachman reported at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

Six events that might have been related to the vaccine were reported in the TIV arm: acute otitis media (two), pharyngitis (two), conjunctivitis, and injection site swelling.

The proportion of children with grade 2 or higher signs and symptoms was similar (19% with LAIV vs. 17% with TIV), as were the proportion of children with grade 3 or higher signs and symptoms (2.5% vs. 0.8%, respectively), and the proportion of those with events possibly related to the vaccines (6.6% vs. 5%, respectively).

Dr. Nachman said that immunogenicity studies are ongoing. A coinvestigator is an employee of MedImmune Inc., manufacturer of FluMist.

SAN FRANCISCO — The live attenuated influenza vaccine known as FluMist is as safe as an inactivated virus vaccine for children who are infected by the human immunodeficiency virus and have CD4 percentages of 15% or greater, according to the findings of a randomized, controlled trial.

Investigators recorded similar toxicity profiles for FluMist and the trivalent inactivated virus (TIV) vaccine that is standard for this population, Dr. Sharon Nachman reported at the annual meeting of the Pediatric Academic Societies.

Prolonged shedding, a major concern, was not observed in either arm of the phase I-II trial, according to Dr. Nachman, chief of pediatric infectious diseases, department of pediatrics, State University of New York at Stony Brook.

“There were no unexpected toxicities or adverse events associated with administration of LAIV [live attenuated influenza virus] or TIV in HIV-positive children in this study,” she said, summarizing 6 months of follow-up on behalf of the Pediatric AIDS Clinical Trials Group.

The investigators randomized 243 HIV-positive children from 5 to 18 years of age at the start of the 2004–2005 flu season: 122 to LAIV and 121 to TIV.

The LAIV arm of the study received the FluMist formulation that is currently approved for healthy children and adults from the ages of 5 to 49 years. The vaccine is delivered intranasally, whereas TIV must be injected.

Entry criteria included a current viral load below 60,000 copies per milliliter. All participants had at least 16 weeks of stable antiretroviral therapy with three different antiretroviral agents from at least two therapeutic classes.

All of the children had been vaccinated with TIV in at least one of the two previous years as well.

“Ethnicity looks exactly like [the] demographic of perinatally infected children across the United States,” Dr. Nachman said.

She described the study arms as evenly matched with respect to mean age (11.4–11.9 years), CD4 percentage (33%–34%), and viral load (2.9 copies/mL in both groups).

Vaccine administration did not lead to clinically significant changes in CD4 count or viral load during the study. Nor were changes in antiretroviral therapy made necessary by vaccination.

Investigators detected influenza shedding in 31 of 115 LAIV recipients (27%) 3 days after they received the vaccine.

By day 28 only 1 of 119 subjects (0.9%) was shedding virus, and the results of a follow-up culture done on day 56 were negative.

During the first 28 days, eight children in the LAIV arm had nine events that may have been related to FluMist administration: fever (one), malaise (one), conjunctivitis (two), acute otitis media (one), sinusitis (one), pharyngitis (one), and lower respiratory tract illness (one). One child was hospitalized and recovered with antibiotic therapy, Dr. Nachman reported at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

Six events that might have been related to the vaccine were reported in the TIV arm: acute otitis media (two), pharyngitis (two), conjunctivitis, and injection site swelling.

The proportion of children with grade 2 or higher signs and symptoms was similar (19% with LAIV vs. 17% with TIV), as were the proportion of children with grade 3 or higher signs and symptoms (2.5% vs. 0.8%, respectively), and the proportion of those with events possibly related to the vaccines (6.6% vs. 5%, respectively).

Dr. Nachman said that immunogenicity studies are ongoing. A coinvestigator is an employee of MedImmune Inc., manufacturer of FluMist.

SAN FRANCISCO — The live attenuated influenza vaccine known as FluMist is as safe as an inactivated virus vaccine for children who are infected by the human immunodeficiency virus and have CD4 percentages of 15% or greater, according to the findings of a randomized, controlled trial.

Investigators recorded similar toxicity profiles for FluMist and the trivalent inactivated virus (TIV) vaccine that is standard for this population, Dr. Sharon Nachman reported at the annual meeting of the Pediatric Academic Societies.

Prolonged shedding, a major concern, was not observed in either arm of the phase I-II trial, according to Dr. Nachman, chief of pediatric infectious diseases, department of pediatrics, State University of New York at Stony Brook.

“There were no unexpected toxicities or adverse events associated with administration of LAIV [live attenuated influenza virus] or TIV in HIV-positive children in this study,” she said, summarizing 6 months of follow-up on behalf of the Pediatric AIDS Clinical Trials Group.

The investigators randomized 243 HIV-positive children from 5 to 18 years of age at the start of the 2004–2005 flu season: 122 to LAIV and 121 to TIV.

The LAIV arm of the study received the FluMist formulation that is currently approved for healthy children and adults from the ages of 5 to 49 years. The vaccine is delivered intranasally, whereas TIV must be injected.

Entry criteria included a current viral load below 60,000 copies per milliliter. All participants had at least 16 weeks of stable antiretroviral therapy with three different antiretroviral agents from at least two therapeutic classes.

All of the children had been vaccinated with TIV in at least one of the two previous years as well.

“Ethnicity looks exactly like [the] demographic of perinatally infected children across the United States,” Dr. Nachman said.

She described the study arms as evenly matched with respect to mean age (11.4–11.9 years), CD4 percentage (33%–34%), and viral load (2.9 copies/mL in both groups).

Vaccine administration did not lead to clinically significant changes in CD4 count or viral load during the study. Nor were changes in antiretroviral therapy made necessary by vaccination.

Investigators detected influenza shedding in 31 of 115 LAIV recipients (27%) 3 days after they received the vaccine.

By day 28 only 1 of 119 subjects (0.9%) was shedding virus, and the results of a follow-up culture done on day 56 were negative.

During the first 28 days, eight children in the LAIV arm had nine events that may have been related to FluMist administration: fever (one), malaise (one), conjunctivitis (two), acute otitis media (one), sinusitis (one), pharyngitis (one), and lower respiratory tract illness (one). One child was hospitalized and recovered with antibiotic therapy, Dr. Nachman reported at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

Six events that might have been related to the vaccine were reported in the TIV arm: acute otitis media (two), pharyngitis (two), conjunctivitis, and injection site swelling.

The proportion of children with grade 2 or higher signs and symptoms was similar (19% with LAIV vs. 17% with TIV), as were the proportion of children with grade 3 or higher signs and symptoms (2.5% vs. 0.8%, respectively), and the proportion of those with events possibly related to the vaccines (6.6% vs. 5%, respectively).

Dr. Nachman said that immunogenicity studies are ongoing. A coinvestigator is an employee of MedImmune Inc., manufacturer of FluMist.

SANTA ANA PUEBLO, N.M. — Whether infected at birth or through risky behavior, youth with human immunodeficiency virus/acquired immunodeficiency syndrome often have psychiatric disorders, Dr. Maryland Pao said at the annual meeting of the Academy of Psychosomatic Medicine.

“HIV is a psychiatric disease. Psychiatric disease increases risk for HIV, and HIV increases risk for psychiatric disease,” said Dr. Pao, deputy clinical director of the National Institute of Mental Health in Bethesda, Md., and coauthor of a 10-year review of psychiatric research on youth and HIV/AIDS (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:728–47).

Although the incidence of AIDS deaths and of vertical transmissions has declined dramatically in the United States, she said, teenagers account for half of new HIV infections and a quarter of new sexually transmitted diseases that are reported annually. More than half of these new infections, 61%, occur in girls, and 56% of newly infected teenagers are African American, according to the Centers for Disease Control and Prevention.

Dr. Pao has reported high rates of psychiatric illnesses in 34 HIV-infected adolescents (Arch. Pediatr. Adolesc. Med. 2000;154:240–4). More than half, 53%, had psychiatric diagnoses before being treated for HIV; 82% had a history of substance abuse; and half had a history of sexual abuse. At the time they were interviewed, 85% had a current disorder, and 44% were depressed.

No large studies have been done in this population, Dr. Pao said, but other small studies also have shown high rates of psychotropic drug use and depression in teens who become infected with HIV.

About 110,000 perinatally infected youths, meanwhile, account for 18% of people living with HIV. Many are sexually active, according to Dr. Pao, and a growing number of girls have become pregnant. “Many of our patients are in their late teens and early 20s. They know they can transmit HIV, but a third of kids don't tell their partners,” she said. “… These kids are not using protection when they are having sex.”

High rates of disruptive behavioral disorders, including attention-deficit hyperactivity disorder, have been documented in children infected perinatally, according to Dr. Pao. However, whether these are a result of the HIV infection, environment, or other factors is not clear.

“Is hyperactivity impulsivity in kids born with HIV? Is that genetic? Is that HIV? Is that the role of environment and poverty?” she asked, adding, “There is something going on in HIV kids.”

In some cases, she said, HIV-infected youth reach sexual maturity without ever having been told why they are taking medications. Parents do not want their children to know they acquired HIV through sex or drugs, so disclosure becomes an issue.

“You would be amazed at how many parents don't want to tell kids what they actually have,” Dr. Pao said. “In some cases, kids think they have a benign virus. They really didn't know all along, and now they are 12, and you have to tell them.

“Once we disclose, there is a lot of depression and anxiety associated with it,” she added. “It is very, very complicated.”

Dr. Pao called for ongoing and consistent support of HIV-infected youth and their families. Among their many needs, she cited psychosocial evaluations, counselors trained in chronic illnesses, continuity, confidentiality, coping skills, and help in finding schools for children with learning disabilities.

HIV prevention programs need to be tailored to adolescents, she added. “They know how it is transmitted and what needs to be done, but they don't translate that into changes in their behavior,” Dr. Pao said. “What do we have to do to change behavior? We are trying to develop more programs sensitive to adolescent issues.”

SANTA ANA PUEBLO, N.M. — Whether infected at birth or through risky behavior, youth with human immunodeficiency virus/acquired immunodeficiency syndrome often have psychiatric disorders, Dr. Maryland Pao said at the annual meeting of the Academy of Psychosomatic Medicine.

“HIV is a psychiatric disease. Psychiatric disease increases risk for HIV, and HIV increases risk for psychiatric disease,” said Dr. Pao, deputy clinical director of the National Institute of Mental Health in Bethesda, Md., and coauthor of a 10-year review of psychiatric research on youth and HIV/AIDS (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:728–47).

Although the incidence of AIDS deaths and of vertical transmissions has declined dramatically in the United States, she said, teenagers account for half of new HIV infections and a quarter of new sexually transmitted diseases that are reported annually. More than half of these new infections, 61%, occur in girls, and 56% of newly infected teenagers are African American, according to the Centers for Disease Control and Prevention.

Dr. Pao has reported high rates of psychiatric illnesses in 34 HIV-infected adolescents (Arch. Pediatr. Adolesc. Med. 2000;154:240–4). More than half, 53%, had psychiatric diagnoses before being treated for HIV; 82% had a history of substance abuse; and half had a history of sexual abuse. At the time they were interviewed, 85% had a current disorder, and 44% were depressed.

No large studies have been done in this population, Dr. Pao said, but other small studies also have shown high rates of psychotropic drug use and depression in teens who become infected with HIV.

About 110,000 perinatally infected youths, meanwhile, account for 18% of people living with HIV. Many are sexually active, according to Dr. Pao, and a growing number of girls have become pregnant. “Many of our patients are in their late teens and early 20s. They know they can transmit HIV, but a third of kids don't tell their partners,” she said. “… These kids are not using protection when they are having sex.”

High rates of disruptive behavioral disorders, including attention-deficit hyperactivity disorder, have been documented in children infected perinatally, according to Dr. Pao. However, whether these are a result of the HIV infection, environment, or other factors is not clear.

“Is hyperactivity impulsivity in kids born with HIV? Is that genetic? Is that HIV? Is that the role of environment and poverty?” she asked, adding, “There is something going on in HIV kids.”

In some cases, she said, HIV-infected youth reach sexual maturity without ever having been told why they are taking medications. Parents do not want their children to know they acquired HIV through sex or drugs, so disclosure becomes an issue.

“You would be amazed at how many parents don't want to tell kids what they actually have,” Dr. Pao said. “In some cases, kids think they have a benign virus. They really didn't know all along, and now they are 12, and you have to tell them.

“Once we disclose, there is a lot of depression and anxiety associated with it,” she added. “It is very, very complicated.”

Dr. Pao called for ongoing and consistent support of HIV-infected youth and their families. Among their many needs, she cited psychosocial evaluations, counselors trained in chronic illnesses, continuity, confidentiality, coping skills, and help in finding schools for children with learning disabilities.

HIV prevention programs need to be tailored to adolescents, she added. “They know how it is transmitted and what needs to be done, but they don't translate that into changes in their behavior,” Dr. Pao said. “What do we have to do to change behavior? We are trying to develop more programs sensitive to adolescent issues.”

SANTA ANA PUEBLO, N.M. — Whether infected at birth or through risky behavior, youth with human immunodeficiency virus/acquired immunodeficiency syndrome often have psychiatric disorders, Dr. Maryland Pao said at the annual meeting of the Academy of Psychosomatic Medicine.

“HIV is a psychiatric disease. Psychiatric disease increases risk for HIV, and HIV increases risk for psychiatric disease,” said Dr. Pao, deputy clinical director of the National Institute of Mental Health in Bethesda, Md., and coauthor of a 10-year review of psychiatric research on youth and HIV/AIDS (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:728–47).

Although the incidence of AIDS deaths and of vertical transmissions has declined dramatically in the United States, she said, teenagers account for half of new HIV infections and a quarter of new sexually transmitted diseases that are reported annually. More than half of these new infections, 61%, occur in girls, and 56% of newly infected teenagers are African American, according to the Centers for Disease Control and Prevention.

Dr. Pao has reported high rates of psychiatric illnesses in 34 HIV-infected adolescents (Arch. Pediatr. Adolesc. Med. 2000;154:240–4). More than half, 53%, had psychiatric diagnoses before being treated for HIV; 82% had a history of substance abuse; and half had a history of sexual abuse. At the time they were interviewed, 85% had a current disorder, and 44% were depressed.

No large studies have been done in this population, Dr. Pao said, but other small studies also have shown high rates of psychotropic drug use and depression in teens who become infected with HIV.

About 110,000 perinatally infected youths, meanwhile, account for 18% of people living with HIV. Many are sexually active, according to Dr. Pao, and a growing number of girls have become pregnant. “Many of our patients are in their late teens and early 20s. They know they can transmit HIV, but a third of kids don't tell their partners,” she said. “… These kids are not using protection when they are having sex.”

High rates of disruptive behavioral disorders, including attention-deficit hyperactivity disorder, have been documented in children infected perinatally, according to Dr. Pao. However, whether these are a result of the HIV infection, environment, or other factors is not clear.

“Is hyperactivity impulsivity in kids born with HIV? Is that genetic? Is that HIV? Is that the role of environment and poverty?” she asked, adding, “There is something going on in HIV kids.”

In some cases, she said, HIV-infected youth reach sexual maturity without ever having been told why they are taking medications. Parents do not want their children to know they acquired HIV through sex or drugs, so disclosure becomes an issue.

“You would be amazed at how many parents don't want to tell kids what they actually have,” Dr. Pao said. “In some cases, kids think they have a benign virus. They really didn't know all along, and now they are 12, and you have to tell them.

“Once we disclose, there is a lot of depression and anxiety associated with it,” she added. “It is very, very complicated.”

Dr. Pao called for ongoing and consistent support of HIV-infected youth and their families. Among their many needs, she cited psychosocial evaluations, counselors trained in chronic illnesses, continuity, confidentiality, coping skills, and help in finding schools for children with learning disabilities.

HIV prevention programs need to be tailored to adolescents, she added. “They know how it is transmitted and what needs to be done, but they don't translate that into changes in their behavior,” Dr. Pao said. “What do we have to do to change behavior? We are trying to develop more programs sensitive to adolescent issues.”

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. Although the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. Although the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. Although the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease than were those who did not become pregnant, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a counterindication to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said. “They become pregnant because they feel physiologically able to.”

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year before their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (48.6% vs. 35.5% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 55.8%), and a cancer classified as estrogen-receptor negative (54.2% vs. 42.5%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (52.5%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38.1% vs. 28.8% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease than were those who did not become pregnant, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a counterindication to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said. “They become pregnant because they feel physiologically able to.”

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year before their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (48.6% vs. 35.5% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 55.8%), and a cancer classified as estrogen-receptor negative (54.2% vs. 42.5%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (52.5%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38.1% vs. 28.8% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease than were those who did not become pregnant, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a counterindication to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said. “They become pregnant because they feel physiologically able to.”

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year before their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (48.6% vs. 35.5% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 55.8%), and a cancer classified as estrogen-receptor negative (54.2% vs. 42.5%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (52.5%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38.1% vs. 28.8% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

ATLANTA — A review of more than 60,000 melanoma patients found that they were more likely to have a sentinel node biopsy and receive adjuvant therapy with a biologic response modifier if they had commercial insurance and were treated at a teaching hospital in a geographic area where these options were more often used.

Sentinel node biopsies were performed significantly more often in the mountain states, compared with all other areas of the United States. Patients in New England were least likely to have the procedure (odds ratio 0.378).

Use of biologic response modifiers such as interferon-α was most prevalent in the west north central states stretching from North Dakota and Minnesota south to Kansas and Missouri. They were used least often in the area directly south, however: the west south central states of Oklahoma, Arkansas, Texas, and Louisiana (odds ratio 0.395).

Patients in the Mid-Atlantic, south Atlantic, and east south central states also were significantly less likely to be treated with an adjuvant biologic response modifier (odds ratios 0.765, 0.786, and 0.465, respectively).

“It turns out that where patients are treated has a large association with how they are treated,” Dr. Julie R. Lange said in an interview at the annual meeting of the American Society of Clinical Oncology, where she presented the results in a poster.

Dr. Lange, of the department of surgery at Johns Hopkins University in Baltimore, extracted the data from the National Cancer Data Base maintained by the American Cancer Society and the American College of Surgeons.

The study used U.S. Census regions to divide the patients by geographic area. Dr. Lange said the database did not distinguish interferon use from other immune therapies in the biologic response modifier category.

She and her colleagues found 61,251 patients, aged 1–69 years, who had surgery for stage I or II melanoma between 1998 and 2002. Among these patients, 36% had a sentinel node biopsy. The procedure was done in 56% of patients with T3 tumors, 46% with T2 tumors, and 42% with T4 tumors, but only 13% of patients with T1 tumors.

The investigators found 10,790 patients who had surgery for node-positive melanoma between 1994 and 2003. More than a third, 38%, were treated with a biologic response modifier: 37% of patients with one positive node and 39% of those with two or more positive nodes.

Sentinel node biopsies and use of biologic therapies were significantly more common at teaching hospitals than at community hospitals and other types of facilities.

Although both of the therapies were most often used in patients with commercial insurance, the difference was not significant for patients insured by a health maintenance organization or managed care. It was significant for those covered by Medicaid or Medicare and those who were covered by other types of insurance or uninsured.

Gender and race did not appear to play a role in whether the patients received either a sentinel node biopsy or a biologic therapy.

Both the biopsy and this kind of treatment were most common in patients under the age of 25. All older patients were significantly less likely to receive a biologic, only patients aged 51–69 years were significantly less likely to have a sentinel node biopsy.

Era of treatment also seemed to have an effect. Patients treated after the year 2000 were more likely to have a sentinel node biopsy than were those treated earlier. Conversely, patients were less likely to receive a biologic therapy if treated after 1998.

“It is not really clear why disparities exist,” Dr. Lange said. “It is one of those studies that raise a lot of questions.”

ATLANTA — A review of more than 60,000 melanoma patients found that they were more likely to have a sentinel node biopsy and receive adjuvant therapy with a biologic response modifier if they had commercial insurance and were treated at a teaching hospital in a geographic area where these options were more often used.

Sentinel node biopsies were performed significantly more often in the mountain states, compared with all other areas of the United States. Patients in New England were least likely to have the procedure (odds ratio 0.378).

Use of biologic response modifiers such as interferon-α was most prevalent in the west north central states stretching from North Dakota and Minnesota south to Kansas and Missouri. They were used least often in the area directly south, however: the west south central states of Oklahoma, Arkansas, Texas, and Louisiana (odds ratio 0.395).

Patients in the Mid-Atlantic, south Atlantic, and east south central states also were significantly less likely to be treated with an adjuvant biologic response modifier (odds ratios 0.765, 0.786, and 0.465, respectively).

“It turns out that where patients are treated has a large association with how they are treated,” Dr. Julie R. Lange said in an interview at the annual meeting of the American Society of Clinical Oncology, where she presented the results in a poster.

Dr. Lange, of the department of surgery at Johns Hopkins University in Baltimore, extracted the data from the National Cancer Data Base maintained by the American Cancer Society and the American College of Surgeons.

The study used U.S. Census regions to divide the patients by geographic area. Dr. Lange said the database did not distinguish interferon use from other immune therapies in the biologic response modifier category.

She and her colleagues found 61,251 patients, aged 1–69 years, who had surgery for stage I or II melanoma between 1998 and 2002. Among these patients, 36% had a sentinel node biopsy. The procedure was done in 56% of patients with T3 tumors, 46% with T2 tumors, and 42% with T4 tumors, but only 13% of patients with T1 tumors.

The investigators found 10,790 patients who had surgery for node-positive melanoma between 1994 and 2003. More than a third, 38%, were treated with a biologic response modifier: 37% of patients with one positive node and 39% of those with two or more positive nodes.

Sentinel node biopsies and use of biologic therapies were significantly more common at teaching hospitals than at community hospitals and other types of facilities.

Although both of the therapies were most often used in patients with commercial insurance, the difference was not significant for patients insured by a health maintenance organization or managed care. It was significant for those covered by Medicaid or Medicare and those who were covered by other types of insurance or uninsured.

Gender and race did not appear to play a role in whether the patients received either a sentinel node biopsy or a biologic therapy.

Both the biopsy and this kind of treatment were most common in patients under the age of 25. All older patients were significantly less likely to receive a biologic, only patients aged 51–69 years were significantly less likely to have a sentinel node biopsy.

Era of treatment also seemed to have an effect. Patients treated after the year 2000 were more likely to have a sentinel node biopsy than were those treated earlier. Conversely, patients were less likely to receive a biologic therapy if treated after 1998.

“It is not really clear why disparities exist,” Dr. Lange said. “It is one of those studies that raise a lot of questions.”

ATLANTA — A review of more than 60,000 melanoma patients found that they were more likely to have a sentinel node biopsy and receive adjuvant therapy with a biologic response modifier if they had commercial insurance and were treated at a teaching hospital in a geographic area where these options were more often used.

Sentinel node biopsies were performed significantly more often in the mountain states, compared with all other areas of the United States. Patients in New England were least likely to have the procedure (odds ratio 0.378).

Use of biologic response modifiers such as interferon-α was most prevalent in the west north central states stretching from North Dakota and Minnesota south to Kansas and Missouri. They were used least often in the area directly south, however: the west south central states of Oklahoma, Arkansas, Texas, and Louisiana (odds ratio 0.395).

Patients in the Mid-Atlantic, south Atlantic, and east south central states also were significantly less likely to be treated with an adjuvant biologic response modifier (odds ratios 0.765, 0.786, and 0.465, respectively).

“It turns out that where patients are treated has a large association with how they are treated,” Dr. Julie R. Lange said in an interview at the annual meeting of the American Society of Clinical Oncology, where she presented the results in a poster.

Dr. Lange, of the department of surgery at Johns Hopkins University in Baltimore, extracted the data from the National Cancer Data Base maintained by the American Cancer Society and the American College of Surgeons.

The study used U.S. Census regions to divide the patients by geographic area. Dr. Lange said the database did not distinguish interferon use from other immune therapies in the biologic response modifier category.

She and her colleagues found 61,251 patients, aged 1–69 years, who had surgery for stage I or II melanoma between 1998 and 2002. Among these patients, 36% had a sentinel node biopsy. The procedure was done in 56% of patients with T3 tumors, 46% with T2 tumors, and 42% with T4 tumors, but only 13% of patients with T1 tumors.

The investigators found 10,790 patients who had surgery for node-positive melanoma between 1994 and 2003. More than a third, 38%, were treated with a biologic response modifier: 37% of patients with one positive node and 39% of those with two or more positive nodes.

Sentinel node biopsies and use of biologic therapies were significantly more common at teaching hospitals than at community hospitals and other types of facilities.

Although both of the therapies were most often used in patients with commercial insurance, the difference was not significant for patients insured by a health maintenance organization or managed care. It was significant for those covered by Medicaid or Medicare and those who were covered by other types of insurance or uninsured.

Gender and race did not appear to play a role in whether the patients received either a sentinel node biopsy or a biologic therapy.

Both the biopsy and this kind of treatment were most common in patients under the age of 25. All older patients were significantly less likely to receive a biologic, only patients aged 51–69 years were significantly less likely to have a sentinel node biopsy.

Era of treatment also seemed to have an effect. Patients treated after the year 2000 were more likely to have a sentinel node biopsy than were those treated earlier. Conversely, patients were less likely to receive a biologic therapy if treated after 1998.

“It is not really clear why disparities exist,” Dr. Lange said. “It is one of those studies that raise a lot of questions.”

SAN DIEGO — Two weeks of continuous positive airway pressure significantly reduced the blood pressure of hypertensive obstructive sleep apnea patients in a small randomized controlled trial presented in a poster at the International Conference of the American Thoracic Society.

Dr. Daniel Norman reported that nighttime systolic, mean arterial, and diastolic blood pressure decreased by 6 mm Hg, 5 mm Hg, and 4 mm Hg, respectively, in 18 patients on continuous positive airway pressure (CPAP).

Daytime mean arterial pressure (MAP) and diastolic blood pressure each declined by 3 mm Hg as well. Though the difference was not statistically significant, daytime systolic blood pressure also dropped by about 2 mm Hg.

“This kind of improvement in blood pressure is similar to what you'd see with many hypertensive medications,” Dr. Norman, a fellow in pulmonary and critical care at the University of California, San Diego Medical Center, said at a press briefing.

Based on these reductions, he added, “You would expect to see improvement in morbidity and mortality.”

In contrast, 24-hour ambulatory blood pressure monitoring revealed no significant improvements in the blood pressure of 13 patients treated with supplemental oxygen or of 15 patients on placebo. The investigators adapted the equipment taken home by patients, so that the assigned apparatus looked the same regardless of which therapeutic option was delivered.

Though patients given supplemental oxygen did have better oxygenation saturation, this did not appear to have an impact on blood pressure, according to Dr. Norman and his coinvestigators in the departments of medicine and psychiatry at the university. They speculated that CPAP's ability to improve blood pressure may involve “mechanisms other than improvement of nocturnal oxyhemoglobin saturation.”

After 2 weeks of therapy, both the CPAP and supplemental oxygen groups registered improvements in average nocturnal saturation of oxyhemoglobin (SpO₂) and average SpO₂ nadir. These values had been similar in all three groups at baseline, but the final SpO₂ values for both CPAP and supplemental oxygen patients were higher than those recorded in patients on placebo.

Apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) scores fell in the groups treated with CPAP or supplemental oxygen, but the investigators reported “the magnitude of change was smaller in the oxygen group and not enough to differentiate it from placebo.”

Dr. Norman noted that obstructive sleep apnea is known to increase the risk of hypertension. He also acknowledged that half of the sleep apnea patients offered CPAP find they cannot tolerate it and seek other therapies, such as supplemental oxygen.

The trial doesn't rule out supplemental oxygen, he commented, “but it reaffirms that CPAP remains the gold standard of therapy.”

The patients in the trial ranged from 25 to 65 years of age with a mean body mass index of 29.5–31.5 kg/m

Mean arterial pressure at baseline was 91.2 mm Hg in the placebo group, 94.9 mm Hg in patients treated with oxygen, and 98.1 mm Hg in the CPAP group. Average diastolic blood pressure was 75.6 mm Hg, 76 mm Hg, and 79.6 mm Hg, respectively.

SAN DIEGO — Two weeks of continuous positive airway pressure significantly reduced the blood pressure of hypertensive obstructive sleep apnea patients in a small randomized controlled trial presented in a poster at the International Conference of the American Thoracic Society.

Dr. Daniel Norman reported that nighttime systolic, mean arterial, and diastolic blood pressure decreased by 6 mm Hg, 5 mm Hg, and 4 mm Hg, respectively, in 18 patients on continuous positive airway pressure (CPAP).

Daytime mean arterial pressure (MAP) and diastolic blood pressure each declined by 3 mm Hg as well. Though the difference was not statistically significant, daytime systolic blood pressure also dropped by about 2 mm Hg.

“This kind of improvement in blood pressure is similar to what you'd see with many hypertensive medications,” Dr. Norman, a fellow in pulmonary and critical care at the University of California, San Diego Medical Center, said at a press briefing.

Based on these reductions, he added, “You would expect to see improvement in morbidity and mortality.”

In contrast, 24-hour ambulatory blood pressure monitoring revealed no significant improvements in the blood pressure of 13 patients treated with supplemental oxygen or of 15 patients on placebo. The investigators adapted the equipment taken home by patients, so that the assigned apparatus looked the same regardless of which therapeutic option was delivered.

Though patients given supplemental oxygen did have better oxygenation saturation, this did not appear to have an impact on blood pressure, according to Dr. Norman and his coinvestigators in the departments of medicine and psychiatry at the university. They speculated that CPAP's ability to improve blood pressure may involve “mechanisms other than improvement of nocturnal oxyhemoglobin saturation.”

After 2 weeks of therapy, both the CPAP and supplemental oxygen groups registered improvements in average nocturnal saturation of oxyhemoglobin (SpO₂) and average SpO₂ nadir. These values had been similar in all three groups at baseline, but the final SpO₂ values for both CPAP and supplemental oxygen patients were higher than those recorded in patients on placebo.

Apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) scores fell in the groups treated with CPAP or supplemental oxygen, but the investigators reported “the magnitude of change was smaller in the oxygen group and not enough to differentiate it from placebo.”

Dr. Norman noted that obstructive sleep apnea is known to increase the risk of hypertension. He also acknowledged that half of the sleep apnea patients offered CPAP find they cannot tolerate it and seek other therapies, such as supplemental oxygen.

The trial doesn't rule out supplemental oxygen, he commented, “but it reaffirms that CPAP remains the gold standard of therapy.”

The patients in the trial ranged from 25 to 65 years of age with a mean body mass index of 29.5–31.5 kg/m

Mean arterial pressure at baseline was 91.2 mm Hg in the placebo group, 94.9 mm Hg in patients treated with oxygen, and 98.1 mm Hg in the CPAP group. Average diastolic blood pressure was 75.6 mm Hg, 76 mm Hg, and 79.6 mm Hg, respectively.

SAN DIEGO — Two weeks of continuous positive airway pressure significantly reduced the blood pressure of hypertensive obstructive sleep apnea patients in a small randomized controlled trial presented in a poster at the International Conference of the American Thoracic Society.

Dr. Daniel Norman reported that nighttime systolic, mean arterial, and diastolic blood pressure decreased by 6 mm Hg, 5 mm Hg, and 4 mm Hg, respectively, in 18 patients on continuous positive airway pressure (CPAP).

Daytime mean arterial pressure (MAP) and diastolic blood pressure each declined by 3 mm Hg as well. Though the difference was not statistically significant, daytime systolic blood pressure also dropped by about 2 mm Hg.

“This kind of improvement in blood pressure is similar to what you'd see with many hypertensive medications,” Dr. Norman, a fellow in pulmonary and critical care at the University of California, San Diego Medical Center, said at a press briefing.

Based on these reductions, he added, “You would expect to see improvement in morbidity and mortality.”

In contrast, 24-hour ambulatory blood pressure monitoring revealed no significant improvements in the blood pressure of 13 patients treated with supplemental oxygen or of 15 patients on placebo. The investigators adapted the equipment taken home by patients, so that the assigned apparatus looked the same regardless of which therapeutic option was delivered.

Though patients given supplemental oxygen did have better oxygenation saturation, this did not appear to have an impact on blood pressure, according to Dr. Norman and his coinvestigators in the departments of medicine and psychiatry at the university. They speculated that CPAP's ability to improve blood pressure may involve “mechanisms other than improvement of nocturnal oxyhemoglobin saturation.”

After 2 weeks of therapy, both the CPAP and supplemental oxygen groups registered improvements in average nocturnal saturation of oxyhemoglobin (SpO₂) and average SpO₂ nadir. These values had been similar in all three groups at baseline, but the final SpO₂ values for both CPAP and supplemental oxygen patients were higher than those recorded in patients on placebo.

Apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) scores fell in the groups treated with CPAP or supplemental oxygen, but the investigators reported “the magnitude of change was smaller in the oxygen group and not enough to differentiate it from placebo.”

Dr. Norman noted that obstructive sleep apnea is known to increase the risk of hypertension. He also acknowledged that half of the sleep apnea patients offered CPAP find they cannot tolerate it and seek other therapies, such as supplemental oxygen.

The trial doesn't rule out supplemental oxygen, he commented, “but it reaffirms that CPAP remains the gold standard of therapy.”

The patients in the trial ranged from 25 to 65 years of age with a mean body mass index of 29.5–31.5 kg/m

Mean arterial pressure at baseline was 91.2 mm Hg in the placebo group, 94.9 mm Hg in patients treated with oxygen, and 98.1 mm Hg in the CPAP group. Average diastolic blood pressure was 75.6 mm Hg, 76 mm Hg, and 79.6 mm Hg, respectively.

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

A total of 22 people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data.

Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. A total of 80% said they had had the FOBT screen for colorectal cancer, she said.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents reported they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The other 136 patients screened positive during routine FOBT.

Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

Complete colon examination is the only screening method that has been shown to reduce the incidence of and mortality from colorectal cancer in randomized trials, according to the investigators.

Dr. Richardson noted that the patient-reported data correspond to previous studies of FOBT follow-up and to physicians surveys in which only 50%–60% of respondents said they recommend total colon examination after an abnormal FOBT.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said.

'The follow-up to [positive fecal occult blood test] screening seems to be a black box.' DR. RICHARDSON

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

A total of 22 people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data.

Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. A total of 80% said they had had the FOBT screen for colorectal cancer, she said.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents reported they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The other 136 patients screened positive during routine FOBT.

Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

Complete colon examination is the only screening method that has been shown to reduce the incidence of and mortality from colorectal cancer in randomized trials, according to the investigators.

Dr. Richardson noted that the patient-reported data correspond to previous studies of FOBT follow-up and to physicians surveys in which only 50%–60% of respondents said they recommend total colon examination after an abnormal FOBT.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said.

'The follow-up to [positive fecal occult blood test] screening seems to be a black box.' DR. RICHARDSON

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

A total of 22 people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data.

Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. A total of 80% said they had had the FOBT screen for colorectal cancer, she said.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents reported they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The other 136 patients screened positive during routine FOBT.

Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

Complete colon examination is the only screening method that has been shown to reduce the incidence of and mortality from colorectal cancer in randomized trials, according to the investigators.

Dr. Richardson noted that the patient-reported data correspond to previous studies of FOBT follow-up and to physicians surveys in which only 50%–60% of respondents said they recommend total colon examination after an abnormal FOBT.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said.

'The follow-up to [positive fecal occult blood test] screening seems to be a black box.' DR. RICHARDSON

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen-receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. While the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen-receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. While the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — New results from the international Herceptin Adjuvant (HERA) trial show that taking trastuzumab for 12 months after standard chemotherapy significantly reduced the risk of death for early-stage HER2-positive breast cancer patients.

At a median follow-up of 2 years, 1,703 patients treated with trastuzumab (Herceptin), a monoclonal antibody, also continued to have better disease-free survival, compared with 1,698 patients in the observation arm of the study.

Risk of cardiotoxicity remained low in the updated data presented by Dr. Ian Edward Smith at the annual meeting of the American Society of Clinical Oncology.

The researchers for the phase III trial, conducted by the Swiss-based Roche pharmaceutical company and the Breast International Group (BIG), previously reported a disease-free survival benefit based on 1-year data (N. Engl. J. Med. 2005;353:1659–72). They have yet to report on a third arm of the study that randomized 1,694 women to 24 months of adjuvant therapy with trastuzumab.

In a discussion of the new data, Dr. Clifford A. Hudis described HERA and other studies of adjuvant trastuzumab as “amazingly consistent.” The value of trastuzumab is established, but the best way to incorporate it into therapy for early-stage human epidermal growth factor receptor 2 (HER2)-positive patients still needs to be resolved, said Dr. Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York.

“Approval and use in the adjuvant setting is appropriate, and we should be working on that at this time,” he said.

In the 2-year data reported by Dr. Smith, head of the breast unit at Royal Marsden Hospital in London, an intent-to-treat analysis found that 92.4% of the trastuzumab arm and 89.7% of the observation group were alive at 3 years (hazard ratio 0.66). Disease-free survival was 80.6% in the trastuzumab arm and 74.3% in the observation group (hazard ratio 0.64).

Dr. Smith reported similar results in a censored analysis that did not count 861 observation arm patients who switched to trastuzumab after the first-year results were announced last year. He predicted the desire of patients to cross over to the treatment arm of a trial that reports significant benefit in its preliminary analysis will be a recurring issue in breast cancer trials.

Only intent-to-treat analysis was presented for the rest of the data. Time to distant recurrence of disease favored trastuzumab: 85.7% did not have distant disease at 3 years vs. 79.4% of the control group (hazard ratio 0.60).

There were more central nervous system events in patients treated with trastuzumab, however. Dr. Smith speculated that trastuzumab may not penetrate the CNS sufficiently or these events might be masked in the observation arm because some of these women had other distant events before brain metastases.

Subgroup analyses of the trastuzumab arm found “no evidence of substantial difference in relative treatment effect between subgroups and no evidence of any subgroup in which there is less efficacy,” Dr. Smith said. He singled out nodal status and neoadjuvant therapy, emphasizing that trastuzumab was equally effective whether the women were lymph node negative or lymph node positive at entry into the trial and whether they had neoadjuvant therapy.

Conducted at 480 sites in 39 countries, the trial allowed wide latitude in the types of prior regimens the women received. Dr. Smith noted that only 26% had prior taxane therapy. About 11% had neoadjuvant therapy.

About half of the women were estrogen-receptor negative, he said, proposing that it may be the largest trial ever conducted in ER-negative women. While the arms were well balanced, he characterized the overall population as young, with a median age of 49 years. Only 16% were over the age of 60.

Not unexpectedly, serious adverse events were more frequent with trastuzumab: 9.2% of patients had at least one, compared with 6.6% of the control group. All told, 172 women (10.1%) on trastuzumab withdrew from treatment.

Although deaths resulting from adverse events were more common in patients on trastuzumab, Dr. Smith said none were related to the drug. The only cardiac death occurred in a patient randomized to observation.

Other measures showed that cardiac toxicity occurred in small proportions of women on trastuzumab: severe congestive heart failure in 0.6%, symptomatic congestive heart failure in 2.1%, and a confirmed significant drop in left ventricular ejection fraction in 3.0%.

“The risk of cardiac toxicity remains low,” Dr. Smith said.

He promised continued safety evaluation in the ongoing long-term follow-up of these patients. Of particular interest, he said, will be data on patients who took trastuzumab for 24 months. The greatest risk of recurrence has been during the first year of the study, and investigators are hoping that longer therapy will be more protective.

Trial sponsor Roche markets trastuzumab internationally and has a majority interest in Genentech Inc., which markets the drug in the United States.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Among the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less. Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway. However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Per E. Lønning (left). ©ASCO/Todd Buchanan

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Among the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less. Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway. However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Per E. Lønning (left). ©ASCO/Todd Buchanan

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Among the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less. Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway. However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Per E. Lønning (left). ©ASCO/Todd Buchanan

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a [contraindication] to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W. Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said.

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these studies may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year prior to their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (49% vs. 36% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 56%), and a cancer classified as estrogen-receptor negative (54% vs. 43%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (53%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38% vs. 29% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

For women with a poor prognosis after breast cancer, 'it is very important to wait 5 years before a pregnancy.' DR. LARGILLIER

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a [contraindication] to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W. Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said.

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these studies may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year prior to their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (49% vs. 36% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 56%), and a cancer classified as estrogen-receptor negative (54% vs. 43%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (53%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38% vs. 29% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

For women with a poor prognosis after breast cancer, 'it is very important to wait 5 years before a pregnancy.' DR. LARGILLIER

ATLANTA — Young women who became pregnant after breast cancer treatment were significantly less likely to have a recurrence or to die of the disease, according to a French retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Rémy Largillier reported that 5-year overall survival was 97% for 118 women who became pregnant after breast cancer, but only 80% for 762 women who did not. The hazard ratio in favor of pregnancy was 0.23.

“Perhaps it is not a [contraindication] to have a pregnancy,” Dr. Largillier, of the Centre Antoine Lacassagne in Nice, and his coinvestigators concluded.

In a discussion of the poster, Dr. Robert W. Carlson, professor of medicine at the cancer center of Stanford (Calif.) University, described the study as important, but cautioned that it was not cause to encourage breast cancer survivors to become pregnant. The positive outcome “may be nothing but a healthy mother effect,” he said.

The take-home message, Dr. Carlson said, is that “pregnancy subsequent to breast cancer does not have a negative impact on breast cancer outcome, and a pregnancy recent to a diagnosis of breast cancer does not independently predict for a poor outcome.”

In conducting the study, the investigators cited the lack of data supporting the decision of many women to wait at least 2 years after breast cancer treatment before they become pregnant. Although some studies have suggested that pregnancy might be protective, Dr. Largillier's group acknowledged that these studies may have been biased by the “healthy mother” effect, in which only women who feel healthy and disease-free choose to become pregnant.

The study reviewed 908 patients younger than age 35 years who were treated for nonmetastatic and unilateral invasive breast carcinoma at eight French hospitals between 1990 and 1999. The women's average age was 31.4 years, and the median follow-up was 87 months.

Included in the analysis were 105 women who gave birth during the year prior to their diagnosis. The investigators found that these women were significantly more likely to have a positive axillary node (49% vs. 36% of those who did not give birth before diagnosis), a tumor staged as T2 or greater (75% vs. 56%), and a cancer classified as estrogen-receptor negative (54% vs. 43%).

Pregnancy in the year before diagnosis increased the risk of death and risk of local recurrence in univariate analysis. Only the relationship to local recurrence persisted in multivariate analysis, however. The hazard ratio was 1.75.

Women who became pregnant after treatment were significantly younger than the rest of the population and less likely to have a family history of breast cancer. More than half (53%) were younger than 30 years of age, compared with 28% of those who did not become pregnant as breast cancer survivors.

The posttreatment mothers also were more likely to have positive axillary nodes (38% vs. 29% of women who did not become pregnant after diagnosis), but their tumor size and estrogen-receptor status were similar to the rest of the population.

Women with good prognoses after completing breast cancer treatment had a low annual risk of distant recurrence that remained constant over time, according to the investigators. This was not the case for the women with poor prognoses: They had a high annual risk of distant recurrence that did not level off for 80 months. After that point, their risk was no greater than the risk for the women with good prognoses.

“In this large study population, pregnancy was not associated with poorer survival,” the investigators concluded, but they advised that for women with poor prognoses after breast cancer treatment, “it is very important to wait 5 years before a pregnancy.”

For women with a poor prognosis after breast cancer, 'it is very important to wait 5 years before a pregnancy.' DR. LARGILLIER