JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives Journals news releases are made available to the public after 3 pm Central time on Mondays. We also provide a list of previous news releases.

(Embargoed for Release: 3 p.m. CT, Tuesday, June 24, 2003)

JAMA NEW RELEASES

   HORMONE THERAPY LINKED TO INCREASED RISK OF BREAST CANCERS, LATER DIAGNOSIS AND MORE ABNORMAL MAMMOGRAMS

   CHILDREN BORN WITH EXTREMELY LOW BIRTH WEIGHT OR VERY PRETERM DISPLAY EDUCATIONAL AND BEHAVIORAL IMPAIRMENTS AT SCHOOL-AGE

   U.S. MILITARY STUDY SHOWS LARGE SCALE SMALLPOX VACCINATION CAN BE CONDUCTED SAFELY, WITH LOW RATE OF SERIOUS SIDE EFFECTS

JAMA REPORT (VIDEO NEWS RELEASE SCRIPT)

   NEW STUDY SHOWS COMBINATION HORMONE THERAPY STIMULATES BREAST CANCER GROWTH AND HINDERS DIAGNOSIS

INFORMATION CONTAINED IN THESE NEWS RELEASES IS PROTECTED BY COPYRIGHT. JOURNAL ATTRIBUTION IS REQUIRED.

TV Note: This week's JAMA video news release is on hormone therapy being linked to an increased risk for breast cancers, later diagnosis and more abnormal mammograms. The release will be fed Tuesday, June 24, from 9:00 - 9:30 a.m. ET on Telstar 6, Transponder 11 (C-Band) and from 2:00 - 2:30 p.m. ET on Telstar 6, Transponder 11 (C-Band). For more information, call 312/464-JAMA (5262).

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), TUESDAY, JUNE 24, 2003
Media Advisory: To contact Rowan T. Chlebowski, M.D., Ph.D., call Chris Lewis at 310/222-4240. To contact Christopher I. Li, M.D., Ph.D., call Kristen Lidke Woodward at 206/667-5095. To contact editorialist Peter H. Gann. M.D., Sc.D., call Elizabeth Crown at 312/503-8928.

"Consideration for use of estrogen plus progestin for any duration by postmenopausal women should incorporate the current findings into established and emerging risks and benefits of these agents," they conclude.
(JAMA. 2003;289:3243-3253. Available post-embargo at jama.com)

Editor's Note: This study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services. The active study drug and placebo were supplied by Wyeth-Ayerst Research Laboratories, Philadelphia, Pa. For the financial disclosures of the authors, please see the JAMA article.

COMBINED ESTROGEN AND PROGESTIN HORMONE THERAPY LINKED WITH INCREASED RISK OF BREAST CANCER, REGARDLESS OF PATTERNS OF USE

In a related article in the June 25 issue of JAMA, researchers found that combined estrogen and progestin hormone therapy (CHT) is associated with an increase in the risk for breast cancer whether the progestin component was taken every day (continuous CHT) or taken only a certain number of days each month (sequential CHT).

According to the article, several studies including the Women's Health Initiative (WHI) indicate that the use of CHT is associated with an increased risk of breast cancer. An analysis of 51 studies found that current users of CHT or progestin alone for 5 years or longer had a 53 percent increase in risk of breast cancer. However, few studies have looked at the effects of long durations of CHT use on breast cancer risk, or the effects of continuous vs. sequential use of the progestin component.

Christopher I. Li, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues investigated the effects of long term CHT use (both continuous and sequential) and estrogen therapy (ET, estrogen alone) in 975 women, 65-79 years old who were diagnosed with invasive breast cancer (between April 1, 1997 through May 31, 1999) and in 1,007 women without breast cancer.

The researchers found that women using estrogen hormone therapy for 25 years or longer, had no significant increase in risk of breast cancer. Women who used CHT (and may have also used estrogen therapy at some point) had a 1.7-fold increased risk of breast cancer, including a 2.7-fold increased risk of invasive lobular carcinoma (a specific type of breast cancer), a 1.5-fold increased risk of invasive ductal carcinoma (another type of breast cancer), and 2-fold increase in breast cancers sensitive to the effects of either estrogen or progestin, (known as ER-positive or PR-positive tumors).

The researchers also found that the increased risk of breast cancer was greatest in women using CHT for longer lengths of time: users for 5-14.9 years and users for 15 or more years had a 1.5-fold increased risk and a 1.6-fold increased risk for invasive ductal carcinoma, respectively, and a 3.7-fold and 2.6-fold increase in risk for invasive lobular carcinoma, respectively). Similar risk patterns were noted in women who took CHT continuously and sequentially.

They write: "Evidence is mounting regarding the adverse impact on breast cancer risk of adding progestin to HRT. This adverse impact appears to be manifest within several years of initiating use of CHRT, and to be similar in magnitude irrespective of the pattern of CHRT use (continuous or sequential), " write the authors. "At least for the forms of CHRT used most commonly by U.S. women in the latter part of the 20th century, including both sequential CHRT and continuous CHRT, an increased incidence of breast cancer must be tallied as a possible consequence."
(JAMA. 2003;289:3254-3263). Available post-embargo at jama.com

Editor's Note: This study was supported by the National Cancer Institute (NCI) through a contract with Fred Hutchinson Cancer Research Center. For the financial disclosures of the authors, please see the JAMA article.

EDITORIAL: COMBINED HORMONE THERAPY AND BREAST CANCER - A SINGLE-EDGED SWORD

In an accompanying editorial, Peter H. Gann. M.D., Sc.D., and Monica Morrow, M.D., of The Feinberg School of Medicine, Northwestern University, Chicago, comment on the papers by Chlebowski et al and Li et al.

Gann and Morrow note, "The study [WHI trial] demonstrates that alteration of a woman's basic hormonal physiology over decades in the interest of long-term disease prevention is fraught with hazard."

"The ability of combined hormone therapy to decrease mammographic sensitivity creates an almost unique situation in which an agent increases the risk of developing a disease while simultaneously delaying its detection," write the authors regarding the research by Chlebowski et al.

They further suggest, "The expanded report from the WHI trial is significant because it strongly suggests that the breast cancers related to estrogen plus progestin use are not 'good' ones, that they occur earlier than expected based on some previous studies, that there are no easily identified subgroups at higher risk, and that, to top it off, women using estrogen plus progestin experience a much higher rate of mammographic abnormalities leading to anxiety and further costly workups."

According to the editorialists, "Experienced observers hesitate to label any biomedical research study as 'definitive,' especially in an area as historically controversial as the study of menopausal hormone therapy. Nevertheless, the WHI trial of estrogen plus progestin therapy is as close to definitive as can be expected," write the authors. "The effort and commitment of the investigators, funding agency, and participants were prodigious. Although the results are clear enough to discourage any future attempt at replication, further research certainly is necessary."

"In the meantime, the message for physicians caring for menopausal patients is clear. The increased risk of breast cancer and the mammographic abnormalities among women in the WHI study provide further compelling evidence against the use of combination estrogen plus progestin hormone therapy," they conclude.
(JAMA. 2003;289:3304-3306). Available post-embargo at jama.com

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: jamaarchmedia{at}ama-assn.org.

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EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), TUESDAY, JUNE 24, 2003
Media Advisory: To contact corresponding author Lex W. Doyle, M.D., email: lwd@unimelb.edu.au

CHICAGO—Children with extremely low birth weight (ELBW) or born very preterm show cognitive, behavioral, and educational impairments at school-age, according to an article in the June 25 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, cognitive deficits, school difficulties, and behavioral problems are often reported for children born with ELBW (birth weight less than1000 grams [2.2 lbs. or 35.3 ounces]) or very preterm (less than 28 weeks' gestation). But previous findings were based on children born before the 1990s, before a number of advances in perinatal intensive care. The outcome of school-age children born in the 1990s with ELBW or very preterm has not been known.

Peter Anderson, Ph.D., of the Murdoch Childrens Research Institute, Melbourne, and Lex W. Doyle, M.D., of the University of Melbourne, Australia, and participants with the Victorian Infant Collaborative Study Group, conducted a study to determine the cognitive, educational, and behavioral outcome of ELBW and very preterm infants born in the 1990s compared with normal birth weight (NBW) controls. The ELBW and very preterm cohort was composed of 298 consecutive survivors born during 1991-1992 in Victoria, Australia. The NBW cohort was composed of 262 randomly selected children with birth weights of more than 2499 grams (5.5 lbs. or 88.2 ounces).

The follow-up rates from birth to 8 years of age for survivors were 92.3 percent (275/298) for the ELBW or very preterm cohort and 85.1 percent (223/262) for the NBW cohort. "The ELBW or very preterm children scored significantly below NBW controls on full-scale IQ and indices of verbal comprehension, perceptual organization, freedom from distractibility, and processing speed. The ELBW or very preterm children performed significantly worse than the NBW cohort on tests of reading, spelling, and arithmetic. Attentional difficulties, internalizing behavior problems, and immature adaptive skills were more prevalent in the ELBW or very preterm cohort," the authors write.

The researchers found that in middle childhood, 55 percent of survivors born ELBW or very preterm in the 1990s were exhibiting a clinically significant neurobehavioral impairment. "... thus it is important that medical and psychosocial interventions that aim to reduce the frequency, magnitude, and impact of these neurodevelopmental impairments are developed and evaluated," the authors conclude.
(JAMA. 2003;289:3264-3272. Available post-embargo at jama.com)

Editor's Note: Editor's Note: This study was supported in part by a grant from Health and Community Services, Victoria, Australia, and the National Health and Medical Research Council, Canberra, Australia.

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: jamaarchmedia{at}ama-assn.org.

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EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), TUESDAY, JUNE 24, 2003
Media Advisory: To contact John D. Grabenstein, R.Ph., Ph.D., or James R. Riddle, D.V.M., M.P.H., call Marianne Coates at 703/681-1698. To contact Sharon E. Frey, M.D., call Joe Muehlenkamp at 314/977-8015. To contact Thomas R. Talbot, M.D., call Clinton Colmenares at 615/322-4747. To contact editorialists Mary E. Wright, M.D., M.P.H., or Anthony S. Fauci, M.D., call the NIAID Communications Office at 301/402-1663.

"Program implementation emphasized human factors: careful staff training, contraindication screening, recipient education, and attention to bandaging. Our experience suggests that broad smallpox vaccination programs may be implemented with fewer serious adverse events than previously believed," the authors conclude.
(JAMA. 2003;289:3278-3282. Available post-embargo at jama.com)

PERSONS PREVIOUSLY VACCINATED FOR SMALLPOX CAN BE SUCCESSFULLY REVACCINATED WITH DILUTED VACCINE

In a related article in this issue of JAMA, Sharon E. Frey, M.D., of the Saint Louis University School of Medicine and National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit, St. Louis, and colleagues evaluated the use of diluted vaccinia virus in previously vaccinated ("non-na‹ve") participants. Since smallpox vaccine has not been widely used in the United States since 1972, it was anticipated that many previously vaccinated persons would exhibit a major reaction to smallpox vaccine.

The study included 80 non-naive participants, randomized to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, and examined for major reactions, which were defined as a vesicular or pustular lesion of the skin or an area of palpable induration surrounding a central lesion following vaccination and measures of viral shedding and antibody titers.

Initial vaccination resulted in a major reaction in 64 of 80 participants in the previously vaccinated groups. "Ninety-five percent of non-na‹ve participants had major reactions in the undiluted group, 90 percent in the 1:3.2 dilution group, 81 percent in the 1:10 dilution group, and 52.6 percent in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions and significantly less incidence of fever. Pre-existing antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants," the researchers write.

"Previously vaccinated persons can be successfully revaccinated with diluted (equal or less than 1:10) smallpox vaccine. Fewer adverse reactions were observed in this study of non-naive participants when compared with events in vaccinia-naive participants, which was probably due to immunologic memory," the authors conclude.
(JAMA. 2003;289:3295-3299). Available post-embargo at jama.com

Editor's Note: The research for this study was funded by a grant from the National Institute of Allergy and Infectious Diseases.

CERTAIN TYPE OF SKIN RASH COMMON FOLLOWING SMALLPOX VACCINATION

Also reported in this issue of JAMA, a small proportion of persons who are vaccinated for smallpox contract folliculitis, a benign skin rash, according to Thomas R. Talbot, M.D., and colleagues from Vanderbilt University School of Medicine, Nashville, Tenn.

The researchers conducted a study to examine the skin eruptions following smallpox vaccination in healthy, vaccinia-na‹ve (not previously vaccinated) adult participants, from October 2002 to March 2003. In previous reports, serious skin rashes directly related to the vaccinia virus have occurred following smallpox vaccination, but other less severe rashes are possible and distinguishing the serious rashes from the less serious ones is important.

During the trial, of 148 volunteers, 4 (2.7 percent) participants developed generalized skin eruptions and 11 (7.4 percent) noted focal skin eruptions. Viral cultures of sample lesions were negative for vaccinia. The result of a skin biopsy sample from 1 case of generalized rash revealed suppurative folliculitis without evidence of viral infection. All lesions resolved without scarring.

"While folliculitis following vaccination resolved fully in our volunteers, required no specific interventions, and showed no apparent residual sequelae, the concern caused by this eruption on the part of the participants and the clinicians was substantial. The potential for misinformation and concern about skin eruptions following smallpox vaccination are important issues. It is hoped that this report will help educate clinicians, reduce anxiety, and provide reassurance to the medical community," the researchers conclude.
(JAMA. 2003;289:3290-3294). Available post-embargo at jama.com

Editor's Note: Funding for the primary vaccine study was provided by the National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID). Salary support for Dr. Talbot was provided by a grant from the Emerging Infections Diseases Cooperative Agreement.

HEART AILMENT POSSIBLE ADVERSE EVENT FROM SMALLPOX VACCINATION

Myopericarditis, which involves the inflammation of the heart muscle or sac surrounding the heart, should be an expected but apparently uncommon adverse event associated with smallpox vaccination, according to an article in this issue of JAMA by Jeffrey S. Halsell, D.O., James R. Riddle, D.V.M., M.P.H., and members of the Department of Defense Smallpox Vaccination Clinical Evaluation Team.

The researchers report on the first 18 cases of probable myopericarditis following smallpox vaccination among otherwise healthy, young adult members of the U.S. military who were vaccinated between mid-December 2002 and March 14, 2003. Despite decades as the standard vaccine for U.S. civilian and military populations, the New York City Board of Health (NYCBOH) strain of vaccinia virus (Dryvax, Wyeth Laboratories, Marietta, Pa) has only rarely been associated with myopericarditis following vaccination. Only 4 cases were reported in the medical literature between 1955 and 1986.

Among 230,734 primary vaccinees, 18 cases of probable myopericarditis after smallpox vaccination were reported (an incidence of 7.8 per 100,000 over 30 days; 1 per 12,819). No cases of myopercarditis following smallpox vaccination were reported among 95,622 vaccinees who were previously vaccinated.

"Based on reports of cardiac events following smallpox vaccination among military and civilian vaccinees, the CDC has recommended additional exemptions based on known cardiac disease or potential risk factors for cardiac disease. These findings are relevant to current policies and guidelines for vaccinating military and civilian populations against smallpox. Although these cases all recovered clinically from their acute illness, the potential long-term consequences must be evaluated to know the true significance of myopericarditis following vaccination.

"Furthermore, these findings suggest that myopericarditis following smallpox vaccination is an expected adverse event. We project a morbidity estimate of at least 78 clinical myopericarditis cases per million primary vaccinees in comparable adult populations. Myopericarditis following vaccination should be considered in the differential diagnosis of patients with chest pain 4 to 30 days following smallpox vaccination," the authors conclude.
(JAMA. 2003;289:3283-3289). Available post-embargo at jama.com

Editor's Note: This study was supported by the Department of Defense, Defense Health Program.

EDITORIAL: SMALLPOX IMMUNIZATION IN THE 21ST CENTURY - THE OLD AND THE NEW

In an accompanying editorial, Mary E. Wright, M.D., M.P.H., and Anthony S. Fauci, M.D., of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Md., write that the four reports in this issue of The Journal highlight the ongoing challenge to clinicians to be mindful of the old while being vigilant for the new.

"Before 2002, virtually all that was known about the efficacy and safety of smallpox vaccination had been documented in studies conducted a minimum of 30 years earlier. This was an era prior to the availability of technological advances, such as flow cytometry, polymerase chain reaction, and magnetic resonance imaging and before modern-day computer systems made it possible to perform diagnostic surveillance and statistical analyses in close to real time. The continued application of these and other new technologies to this historic public health issue should be of great value in furthering the understanding of the nature of smallpox protection induced by vaccination," they write.

"By rapidly sharing the data from their smallpox vaccination experience with the general medical community, the Department of Defense has provided the civilian population with critical information pertaining to an important general public health issue and should be commended for this effort. This is a model for how military and civilian cooperation can effectively serve the public health of the entire nation," they authors conclude.
(JAMA. 2003;289:3306-3309). Available post-embargo at jama.com

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: jamaarchmedia{at}ama-assn.org.

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