Several studies have revealed a possible association between antibiotic use and breast cancer in the Western population of women. However, its association with the Asian population remains unclear. Data utilized in this nationwide population-based retrospective cohort study were obtained from the Korean National Health Insurance Service database. The study population consisted of 4,097,812 women who were followed up from January 1, 2007, to December 31, 2019. Cox proportional hazards regression was utilized to calculate adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the risk of breast cancer according to cumulative days of antibiotic use and the number of antibiotic classes used. It was discovered that women who used antibiotics for more than 365 days had a higher risk of breast cancer (aHR, 1.15
95% CI, 1.09-1.21) in comparison with those who did not use antibiotics. In addition, an association was found among women who used five or more classes of antibiotics, showing a higher risk of breast cancer (aHR, 1.11
95% CI, 1.05-1.17) compared with nonusers. Furthermore, compared with antibiotic nonusers, only users of cephalosporins (aHR, 1.09
95% CI, 1.02-1.17) and lincosamides (aHR, 1.70
95% CI, 1.20-2.42) had a higher risk of breast cancer. These findings support epidemiologic evidence that long-term use of antibiotics may be associated with a higher risk of breast cancer. This underscores the need for further studies to address the potential for residual confounding, confirm causation, and elucidate the underlying mechanisms. Prevention Relevance: This study found a probable duration-dependent association between antibiotic prescriptions and breast cancer risk. The findings indicate that long-term antibiotic use could be associated with an increased risk of breast cancer and highlight the need for further research to confirm causality and mechanisms.