A study released this week lends further support to previous findings of an association between regular aspirin use and reduced risk of breast cancer. The findings, however, come with a few new twists: Aspirin's effect seems to be significantly affected by hormone-receptor status and frequency of use, with the most benefit seen in women with either estrogen- or progesterone-positive tumors and who took aspirin at least seven times a week for at least 6 months.

In the case-controlled study, published in the May 25 Journal of the American Medical Association, the research team, led by Dr. Mary Beth Terry, an epidemiologist at Columbia University, analyzed data from women participating in the Long Island Breast Cancer Study Project, which is funded by the National Cancer Institute and National Institute of Environmental Health Sciences. They collected data on 1,442 women diagnosed with in situ or invasive breast cancer between August 1, 1996 and July 31, 1997, and compared them with 1,420 controls. Overall, 301 case patients and 345 controls reported regular use of aspirin for at least 6 months.

Regular aspirin use was associated with a 20 percent reduced risk compared with nonuse. An even greater risk reduction (28 percent) was seen among women who took at least seven aspirin per week. When results were separated out by hormone-receptor status, only estrogen-receptor negative/progesterone-receptor negative status failed to show a benefit. Aspirin showed the strongest effect, while ibuprofen use had a weaker preventive impact. Acetaminophen showed no protective effects.

The study from Dr. Terry and colleagues builds on preclinical models showing that drugs such as aspirin inhibit cyclooxygenase, or COX, a key player in the synthesis of prostaglandins, which in turn stimulate the production of estrogen. Because of the role estrogen is thought to play in breast cancer development, increasing attention has been paid to ways to interfere with its activity or inhibit its production.

"This is an important finding because it reinforces that estrogen is a key biological contributor to breast cancer risk," says Dr. Deborah Winn, chief of the Clinical and Genetic Epidemiology Research Branch in the NCI Division of Cancer Control and Population Sciences. Dr. Winn also is the NCI program coordinator for the Long Island Breast Cancer Study Project.

Although frequency of aspirin use appeared to outmatch duration in this study, it is unclear how concrete that finding is, says Dr. Ernie Hawk, chief of the Gastrointestinal and Other Cancers Research Group in the NCI Division of Cancer Prevention. Frequency of use is clearly important, he explains, but other studies that found aspirin use reduced the risk of colorectal cancer suggested that duration also is a significant factor.

In addition, no data on aspirin dosage were collected beyond number of tablets per week, something that both Drs. Winn and Hawk agreed further limits interpretation of the study's implications for aspirin use in the prevention of breast cancer.

Several ongoing studies may provide further insights. One study that should provide some "definitive evidence," adds Dr. Hawk, is the Women's Health Study, which has randomized almost 40,000 women to assess the impact of low-dose aspirin, vitamin E, a combination of both agents, or neither on women's risk of cardiovascular disease and cancer.