Science

Christine M. Velicer, PhD Susan R. Heckbert, MD, PhD Johanna W. Lampe, PhD, RD John D. Potter, MD, PhD Carol A. Robertson, RPh Stephen H. Taplin, MD, MPH

Context: Use of antibiotics may be associated with risk of breast cancer through effects on immune function, inflammation, and metabolism of estrogen and phyto-chemicals; however, clinical data on the association between antibiotic use and risk of breast cancer are sparse.
Objective: To examine the association between use of antibiotics and risk of breast cancer.
Design, Setting,and Participants: Case-control study among 2266 women older than 19 years with primary, invasive breast cancer (cases) enrolled in a large, non-profit health plan for at least 1 year between January 1, 1993, and June 30, 2001, and 7953 randomly selected female health plan members (controls), frequency-matched to cases on age and length of enrollment. Cases were ascertained from the Surveillance, Epidemiology, and End Results cancer registry. Antibiotic use was ascertained from computerized pharmacy records.
Main Outcome Measure: Association between extent of antibiotic use and risk of breast cancer.
Results: Increasing cumulative days of antibiotic use were associated with increased risk of incident breast cancer, adjusted for age and length of enrollment. For categories of increasing use (0, 1-50, 51-100, 101-500, 501-1000, and greater than 1001 days), odds ratios (95% confidence intervals) for breast cancer were 1.00 (reference), 1.45 (1.24-1.69), 1.53 (1.28-1.83), 1.68 (1.42-2.00), 2.14 (1.60-2.88), and 2.07 (1.48- 2.89)(Pless than .001 for trend). Increased risk was observed in all antibiotic classes studied and in a subanalysis having breast cancer fatality as the outcome. Among women with
the highest levels of tetracycline or macrolide use, risk of breast cancer was not elevated in those using these antibiotics exclusively for acne or rosacea (indications that could be risk factors for breast cancer due to altered hormone levels), compared with
those using them exclusively for respiratory tract infections, adjusted for age and length of enrollment (odds ratio, 0.91; 95% confidence interval, 0.44-1.87).
Conclusions: Use of antibiotics is associated with increased risk of incident and fatal breast cancer. It cannot be determined from this study whether antibiotic use is causally related to breast cancer, or whether indication for use, overall weakened immune function, or other factors are pertinent underlying exposures. Although further studies are needed, these findings reinforce the need for prudent long-term use of antibiotics.