NEJM Issues Correction to Rofecoxib Polyp Study The editors of the New England Journal of Medicine (NEJM) issued a correction to the statistical analysis of a study, published in March 2005, on cardiovascular events associated with the use of rofecoxib (Vioxx) in the prevention of colon polyp recurrence. The correction, published in the July 13 NEJM, involved a test for proportionality of hazards in which the authors had erroneously used linear time rather than the logarithm of time that was specified in the study's "Methods" section. Initial results from the trial (Adenomatous Polyp Prevention on Vioxx or APPROVe trial) showed that "use of rofecoxib was associated with an increased cardiovascular risk," which prompted Merck's voluntary recall and market removal of the drug in 2004. The incorrect analysis indicated that the increased risk of thrombotic events in the Vioxx group, compared with the placebo group, did not occur until 18 months after treatment began. The corrected analysis casts doubt on the initial conclusion that the relative risk of cardiovascular events changes over time. In an interview with Medscape, NEJM Executive Editor Dr. Gregory Curfman contended that "our editing procedures are rigorous, tight, and vigilant" but that the initial statistical errors in the study were "not something that could have been picked up by a review panel."

Removal of Ovaries Reduces Cancer Risk in Women with BRCA Mutations

Prophylactic surgery to remove the fallopian tubes and ovaries of women who have mutations in the BRCA1 and BRCA2 genes reduces the risk of ovarian, fallopian tube, and peritoneal cancers by 80 percent, researchers report in the July 12 Journal of the American Medical Association (JAMA).

Women who carry mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of ovarian cancer (ranging from 15 to 54 percent). These women are often advised to have their ovaries and fallopian tubes removed as a preventive measure in a procedure called a bilateral salpingo-oophorectomy.

To assess the potential benefits of the procedure, the researchers studied 1,828 women from different countries and followed them on average for 3.5 years. This is the largest prospective study to date of women with BRCA gene mutations that examines the risks of these cancers in women with and without ovaries.

"The study supports the recommendation for prophylactic oophorectomy as a highly effective means of reducing the risk of ovarian and fallopian tube cancer in BRCA1 and BRCA2 carriers," write Dr. Steven Narod of the Centre for Research in Women's Health in Toronto and his colleagues in the Hereditary Ovarian Cancer Clinical Study Group.

Based on the incidence rates they calculated, the researchers estimate that the risk of ovarian cancer is 62 percent for BRCA1 mutation carriers and 18 percent for BRCA2 mutation carriers in women up to age 75 with both ovaries intact. The highest incidence rate was observed for BRCA1 mutation carriers between the ages of 60 and 70 years.

Raloxifene Does Not Protect Women from Coronary Heart Disease

Results from the international Raloxifene Use for The Heart (RUTH) trial published in the July 13 New England Journal of Medicine indicate that raloxifene, a drug that binds to the estrogen receptor and can reduce the risk of invasive breast cancer, does not protect women from coronary heart disease (CHD) as had been predicted.

Investigators from 177 institutions in 26 countries randomly assigned 10,101 postmenopausal women with CHD or at risk for CHD to receive a daily dose of either raloxifene or a placebo. Women took the drugs for a median of approximately 5 years, and were followed for a median of 5.5 years with electrocardiography, serum lipid level analysis, mammograms, and clinical breast examinations.

No significant differences were seen between groups in the incidence of coronary events, including nonfatal myocardial infarction and death from coronary causes. The treatment effect did not differ between subgroups divided by factors such as age and presence of risk factors for CHD. Raloxifene did reduce the incidence of invasive breast cancer in all subgroups of women receiving the drug, but also increased the incidence of fatal stroke and venous thromboembolism.

Because raloxifene reduced the risk of breast cancer, the authors stress the need for risk/benefit analysis for individual patients, concluding that "when considering the use of raloxifene in a postmenopausal woman, the clinician should take into account the individual woman's risk of disease and her personal preferences, and weigh potential benefits against risks and against the availability of alternative interventions."

An accompanying editorial by Dr. Marcia Stefanick of the Stanford University School of Medicine reinforces this point: "These results underscore that both absolute benefits and absolute risks will vary depending on the risk profiles of women receiving treatment (i.e., those at high risk for breast cancer as compared with those at high risk for a coronary event)."

Weight Gain Increases Risk of Breast Cancer After Menopause

Gaining weight after age 18, specifically after menopause, increases a woman's risk of breast cancer after menopause, whereas losing weight after menopause can reduce the risk, researchers at Harvard Medical School have found. They say that many cases of breast cancer could be avoided by women losing weight after menopause.

The researchers suggest that women should be advised to avoid weight gain during adulthood to decrease their postmenopausal breast cancer risk. Hormones are directly related to breast cancer risk, and associations found in the study may be explained in part by the effect of gaining weight on hormones, the researchers report in the July 12 JAMA.

Dr. A. Heather Eliassen and her colleagues tracked participants in the Nurses' Health Study. To assess weight change since age 18, they followed 87,000 women for up to 26 years. They followed 49,500 women for up to 24 years to assess weight change since menopause.

Among the women, 4,400 had invasive breast cancer. After adjusting for multiple breast cancer risk factors, the researchers found that women who gained 55 lbs. or more after age 18 had almost 1½ times the risk of cancer compared with those who maintained their weight. A gain of 22 lbs. after menopause was associated with an increased risk of 18 percent. Losing 22 lbs. after menopause decreased the risk by 57 percent.

"Although these data suggest that it is never too late to lose weight to decrease risk, given the difficulty in losing weight, the emphasis must also remain on weight maintenance throughout adult life," they conclude.

Skin Cancer Campaign Motivates Screening in Men over 50

Community education programs increased the skin cancer screening rates in men over the age of 50, according to study results published online July 10 in Cancer. Men over 50 represent nearly half of all deaths from melanoma in developed countries, but are the least likely group to be screened.

Researchers at the Viertel Centre for Research in Cancer Control in Brisbane, Australia, conducted a randomized, controlled trial to evaluate the effectiveness of a community-based melanoma education and screening program. The researchers studied 18 communities in Queensland, Australia, with adult populations of more than 2,000 people. Nine communities were randomly selected to participate in a 3-year public education campaign that included community and physician education on early screening and dedicated skin-screening clinics. The other nine communities received no intervention. The researchers evaluated the screening behavior and outcomes of men over 50 through telephone surveys at the beginning and end of the trial and 2 years after the intervention.

The study found that men over 50 who participated in the intervention program increased their rate of whole-body clinical skin examinations by fourfold and their rate of skin self-examinations by twofold. Two years after the intervention, men were still twice as likely to report conducting whole-body clinical skin examinations. The authors note that "to sustain screening rates in men 50 years and older, an understanding of their susceptibility to melanoma and their doctor's encouragement of early detection and screening behavior will be important."