MEDICATIONS: LONG-TERM USE OF ANTIBIOTICS POSSIBLY LINKED WITH INCREASED RISK OF BREAST CANCER

February 18, 2003 — Women who used increased amounts of antibiotics appear to have a greater risk of breast cancer, according to a new study in the February 18 issue of The Journal of the American Medical Association. However, the researchers point out that more studies are needed to determine if the association between breast cancer and antibiotics is causal or if there are other underlying factors to be considered.

"Breast cancer is the most frequently diagnosed nonskin malignancy and the second leading cause of cancer mortality in U.S. women," according to background information from the authors. "It is also the most common cancer in women worldwide, with more than 1 million cases diagnosed each year. Antibiotics are used extensively and overused in many countries, though efforts are underway to curb overuse."

Christine M. Velicer, Ph.D., from the University of Washington, Seattle, and colleagues, examined the association between use of antibiotics and the risk of breast cancer by reviewing medical data from 10,219 women enrolled at Group Health Cooperative (GHC), a large nonprofit health plan in western Washington State. (Dr. Velicer is now on staff at the GHC Center for Health Studies, Seattle.) The study cases included 2,266 women older than 19 years with primary, invasive breast cancer enrolled in the health plan, and 7,953 randomly selected female health plan members who did not have breast cancer in the control group. Data on antibiotic use were obtained from the GHC pharmacy database. The researchers looked at the cumulative number of days of antibiotic use and the total number of antibiotic prescriptions for each study participant.

"We found that increasing cumulative days of antibiotic use and increasing cumulative number of antibiotic prescriptions were associated with increased risk of incident breast cancer, after controlling for age and length of enrollment," the researchers state. For example, compared to women who had used no antibiotics, the researchers found that women who had cumulatively used antibiotics for one to 500 days had an associated increased risk of about one-and-a-half times of incident breast cancer. "Increasing cumulative days of antibiotic use was also associated with death due to breast cancer, controlling for age, length of enrollment, and ever use of postmenopausal hormones. All classes of antibiotics were associated with increased risk." The researchers also looked at a subset of study participants with heavy use of macrolide and tetracycline antibiotics and found no difference in risk of incident breast cancer among women using these antibiotics for acne and/or rosacea compared with women using these drugs for respiratory tract infections.

In conclusion, the authors write: "While the implications for clinical practice will not be clear until additional studies are conducted, the results of this study support the continued need for prudent long-term use of antibiotics and the need for further studies of the association between antibiotic use and cancer risk."

Editor's Note: This work was supported in part by grants from the National Cancer Institute and the Gustavus and Louise Pfeiffer Research Foundation.

Editorial: Antibiotics and Breast Cancer

In an accompanying editorial, Roberta B. Ness, M.D., M.P.H., and Jane A. Cauley, Dr.P.H., from the University of Pittsburgh, examine the findings of this study that the use of prescribed antibiotics may be another risk factor for cancer.

"This observation is potentially worrisome in that antibiotic exposure is common and sometimes nonessential. Thus, if real, the risk of breast cancer attributable to the use of antibiotics could be large and partially preventable," the authors write. However, the editorial authors write that the study raises several concerns, including the question of confounding factors in the breast cancer cases cited in the study and the effects of the biological mechanisms of the antibiotics.

"As is often true for reports of new associations, this study provides many (or more) questions than answers. Is the observed link between use of antibiotics and risk of breast cancer confounded by unmeasured factors? Is the effect due to use of antibiotics or to the indications for antibiotics? Does the link suggest caution in the use of antibiotics or suggest that infections at distant sites might promote inflammation localized to the breast? And, whether antibiotics are markers of inflammation or are themselves contributors to carcinogenesis, is use of antibiotics a risk factor for cancers at other sites?

Time and further scrutiny will tell. While more research is needed, this study raises the possibility that long-term use of antibiotics may have harmful consequences, especially for patients for whom other therapeutic options are available."