Table 1.

Summary of the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the natural history of breast cancer. E = Evidence according to the Oxford grading system, levels of evidence; R = recommendation by the authors according to the AGO recommendation system [61, 62]

Drug	BC risk	BC recurrence	Receptor status	Histological type	Survival
Aspirin (AS)	women regularly consuming AS had an about 20% lower risk of BC [2] (prospective cohort study, 26,580 postmenopausal women, E: IB, R:+)	AS was associated with a decreased risk of distant recurrence [51, 52] (prospective study 27,426 women, E: IB, R:+)	i) women who used AS regularly had a similar reduction in both estrogen receptor (ER)+ and ER- BC [31] (case study, 1,170 women, E: III, R:+/–) ii) AS was associated with reduced risks for both HER2+ and HER2- BC [31] (case study, 1,170 women, E: III, R:+/–)	AS was associated with a 41% reduction in risk of luminal A BC and a 48% reduction in risk of triple-negative BC [31] (case study, 1,170 women, E: III, R:+/–)	Nurses’ Health Study suggested a reduced risk of BC mortality and all-cause mortality for women reporting AS use after BC [51] (prospective study 27,426 women, E: IB, R:+)
Non-AS NSAIDs	no association between the use of non-AS NSAIDs with the risk of BC [2] (prospective cohort study, 26,580 post-menopausal women, E: IB, R:+)	regular use of ibuprofen (IB) was associated with a statistically significant decreased risk of BC recurrence [46] (prospective study, 2,292 early-stage BC survivors, E: IIA, R:+)	i) IB users had a statistically significant increased risk of ER+/progesterone receptor (PR)+, but not ER+/PR–, ER–/PR+, or ER-/PR- BC compared to non-users [31] (case study, 1,170 women, E: III, R:+/–) ii) IB was suggestive of a 50% reduction in the risk of HER2-expressing tumors [31] (case study, 1,170 women, E: III, R:+/–)	i) IB was not associated with the risk of triple-negative BC [31] (case study, 1,170 women, E: III, R:+/–) ii) IB was associated with an increased risks of luminal A and luminal B BC [31] (case study, 1,170 women, E: III, R:+/–)	Iowa Women's Health Study showed that ever use of any NSAID after diagnosis was associated with a statistically significant reduction in all-cause mortality and a non-significant reduction in BC mortality [50] (prospective study, 591 postmenopausal women, E: IB, R:+)
Selective COX-2 inhibitors	no reduced risk of BC associated with ever vs. never/rare use [25] (case study, 8,195 BC cases, E: III, R:+/–)	no statistically significant effect on recurrence risk [46] (prospective study, 2,292 early-stage BC survivors, E: IIA, R:+)	–	–	no benefit [48] (case study, 1,024 primary invasive BC cases, E: III, R:+/–)