Twenty-six studies were included in the review (n=528,705 women); 16 case control studies (seven hospital-based and nine population-based) and ten cohort studies.
Overall the number of cases of breast cancer were unaffected by exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (RR 0.94, 95% CI 0.88 to 1.00). Heterogeneity was high (I2=92%), so subgroup analyses were carried out.
Study and NSAID type: Individual analysis of case control and cohort studies indicated no significant reduction in risk. Both ibuprofen (RR 0.81, 95% CI 0.67 to 0.97; seven studies, n=unknown) and aspirin (RR 0.91, 95% CI 0.85 to 0.98; 20 studies, n=unknown) were found to significantly reduce the risk of breast cancer.
Duration and frequency of NSAID use: Statistically significant reduction in the risk of breast cancer was found if NSAIDs were taken daily (RR 0.88, 95% CI 0.79 to 0.99; seven studies, n=unknown) or more than four time per week (RR 0.84, 95% CI 0.74 to 0.94; nine studies, n=unknown). Less than daily use or less than four times a week use had no significant effects on risk. No significant risk was observed for exposure durations of greater than five years or less than five years.
Heterogeneity was high for all studies (I2>74%). Publication bias was found for the overall effect of any NSAID on breast cancer risk (p<0.01) and the adjusted results gave a risk ratio of 1.01 (95% CI 0.96 to 1.07), indicating that there was no association.