Use of antibiotics may be associated with risk of breast cancer through
effects on immune function, inflammation, and metabolism of estrogen and phytochemicals;
however, clinical data on the association between antibiotic use and risk
of breast cancer are sparse.
To examine the association between use of antibiotics and risk of breast
Design, Setting, and Participants
Case-control study among 2266 women older than 19 years with primary,
invasive breast cancer (cases) enrolled in a large, nonprofit 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.
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
≥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) (P<.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).
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.