Infection protection and breast cancer

In first U.S. study, Group Health, Fred Hutchinson researchers find antibiotic use may be associated with increased risk of breast cancer
Researchers found that women who had received more than 25 antibiotic prescriptions over 17 years doubled their risk of developing breast cancer. Graphic by Todd McNaught

Women with high levels of antibiotic use may have twice the risk of developing breast cancer as those who have not used antibiotics, according to a new study conducted by researchers at Group Health Cooperative, Fred Hutchinson and colleagues at the University of Washington and the National Cancer Institute (NCI). The findings appear in the Feb. 18 issue of the Journal of the American Medical Association (JAMA).

Breast-cancer risk doubled among women who had taken antibiotics for more than 500 days or had more than 25 prescriptions over an average of 17 years. But even those who had received between one and 25 antibiotic prescriptions during the same time period had a 50 percent greater breast-cancer risk. What's more, the researchers found risk increased regardless of the type of antibiotic. The findings stem from an analysis of computerized pharmacy records of more than 10,000 members of Group Health Cooperative, a nonprofit health-maintenance organization in Washington state.

The study did not address whether antibiotics themselves cause the increased risk or whether those who need antibiotics have underlying conditions, such as a weaker immune system or specific infections, which might cause breast cancer. The study also did not examine whether antibiotic use is associated with other types of cancer.

Because the analysis is the first of its kind in the United States, more research is needed before the safety of antibiotic use is questioned, said Dr. Christine Velicer, an investigator at Group Health's Center for Cooperative Studies and lead author of the paper.

"Antibiotics have a substantial health-care benefit when they are used prudently to treat bacterial infections, " she said. "If women have concerns about antibiotic use, they should talk with their doctors. But based on this study alone, we would not at this time recommend changes in antibiotic use." She also noted that the comparison group — women who have never used antibiotics, at least during the study period, which averaged 17 years — could have unusual characteristics that offer some protection against cancer.

"Never-users may represent a very unique group that have stronger immune function, for example," she said. "That is another reason that we need to follow up with more research."

Dr. John Potter, Public Health Sciences Division director and a coauthor of the paper, also urged caution regarding the study's implications and reminded women of the value of breast-cancer screening.

"This is an important finding because the study design is strong, the findings are internally consistent, and there is a dose-response relationship evident," he said. "But the findings need to be replicated before we go any further. So in relation to a woman's risk for breast cancer, she should go on doing exactly the sorts of things that she hopefully is already doing — having regular mammograms, remaining physically active and not gaining weight after menopause, as well as consulting with her doctor appropriately.

"Antibiotics are an extremely useful tool for the treatment of infection but should not be misused, such as for treatment of the common cold," he said. "At this stage in the research, these findings are not the basis for personal medical decisions or policy recommendations."

Only one prior study in Finland has examined the link between antibiotic use and breast cancer. That analysis, which was limited to women who self-reported their use of antibiotics for urinary-tract infections, also found that breast-cancer risk was elevated, but the increased risk was limited to premenopausal women.

Velicer said that broader, more thorough studies than the Finnish one to examine the link between antibiotic use and cancer have only recently been possible.

"It's very difficult for people to remember their antibiotic use," she said. "We were able to take advantage of Group Health's pharmacy database, which contains detailed records of the type, dosage and duration of a member's prescription drug use. We were able to link this information to the cancer registry to identify women who had been diagnosed with breast cancer."

The study involved 2,266 women age 20 or older with invasive breast cancer who were enrolled at Group Health for at least one year between 1993 and 2001, and 7,953 randomly selected health-plan members of the same age group who did not have breast cancer. Breast-cancer cases were identified through the Cancer Surveillance System, an NCI-sponsored registry housed in the PHS Division that collects information on cancer cases in western Washington.

Antibiotic use was determined through Group Health's pharmacy database. More than 70 percent of the women in the study had received between one and 25 antibiotic prescriptions. Only 18 percent of women had not used antibiotics.

Researchers found that the risk of breast cancer increased with greater use of antibiotics. In the general population, about one in eight women will develop breast cancer during their lifetime. The current study was not designed to determine how this absolute risk might be altered by antibiotic use. Other studies are needed to establish whether this is a causal relationship and, if so, to determine the magnitude of the overall risk.

One possible explanation for how antibiotics could cause cancer is by changing the makeup of the normal bacteria that live in the bowel. Antibiotics work by selectively killing bacteria while sparing human cells. In addition to acting against infection-causing bugs, antibiotics also can kill the microbes that normally inhabit the gut and help to digest many plant-based foods that may protect the body from cancer.

"There are some protective compounds in the diet that are made effective when they are acted upon by the bugs in the gut," Potter said. "If you disrupt the bugs in the gut with antibiotics, they are no longer available to be effective."

Among the beneficial plant-produced compounds are phytoestrogens, chemicals related to human forms of the hormone estrogen that researchers suspect may protect against breast cancer.

Another way antibiotics might lead to cancer is by altering the body's inflammatory response.

"Antibiotics have a tendency to increase inflammation," Potter said. "We know that inflammation is part of our body's defense mechanism, but inflammation can also be cancer provoking."

The researchers plan to explore both possible mechanisms in future studies, which they hope will shed more light on the medical implications of this initial finding. If either or both possibilities are found to be true, the scientists expect that antibiotics will be found to be associated with increased risk of other types of cancer.

"Right now we want to understand the science behind this finding," Potter said. "The impact on medical practice should come only after we know that this has been replicated in several more studies."

Coauthors included Dr. Susan Heckbert, UW Department of Epidemiology; Carol Robertson of Group Health Cooperative; Dr. Johanna Lampe, investigator in the Public Health Sciences Division; and Dr. Stephen Taplin, an NCI investigator. The work was funded by the National Cancer Institute and the Gustavus and Louise Pfeiffer Research Foundation.

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