Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

Table 3 Associations of NSAID recurrent use with breast cancer, according to characteristics of use (E3N cohort, 2004–2014)

Characteristics of exposure	No. of cases	HR¹ (95% CI)	P_trend²
Cumulative number of DDDs			*0.67*
Never/occasional use of NSAIDs	1441	1 (reference)
≤ 200	763	1.02 (0.93–1.12)
> 200 to ≤ 400	89	0.93 (0.75–1.16)
> 400 to ≤ 600	22	1.28 (0.84–1.95)
> 600	43	1.02 (0.75–1.39)
Unknown	506	0.96 (0.91–1.13)
Cumulative duration of use, months			*0.92*
Never/occasional use of NSAIDs	1441	1 (reference)
≤ 3	516	1.00 (0.91–1.11)
> 3 to ≤ 6	256	1.05 (0.91–1.20)
> 6 to ≤ 12	89	1.02 (0.82–1.27)
> 12	73	1.03 (0.81–1.31)
Unknown	489	0.96 (0.87–1.07)
Time since first use, years			*0.85*
Never/occasional use of NSAIDs	1441	1 (reference)
≤ 4	491	1.00 (0.90–1.11)
> 4 to ≤ 6	201	1.07 (0.92–1.25)
> 4 to ≤ 8	138	1.04 (0.86–1.25)
> 8	249	0.88 (0.76–1.02)
Unknown	344	1.01 (0.90–1.14)
Age at first use, years			*0.85*
Never/occasional use of NSAIDs	1441	1 (reference)
≤ 60	461	0.97 (0.86–1.09)
> 60 to ≤ 65	292	1.06 (0.93–1.22)
> 65 to ≤ 70	215	1.03 (0.88–1.20)
> 70	154	1.03 (0.85–1.24)
Unknown	301	0.95 (0.83–1.09)
Time since last use, years			*0.79*
Never/occasional use of NSAIDs	1441	1 (reference)
Current use	845	1.01 (0.93–1.11)
> Current use to ≤ 2	330	1.02 (0.91–1.16)
> 2 to ≤ 5	103	0.99 (0.81–1.22)
> 5	57	0.85 (0.65–1.11)
Unknown	88	0.89 (0.72–1.11)
Average daily dose			*0.18*
Never/occasional use of NSAIDs	1441	1 (reference)
≤ 1 DDD	445	1.03 (0.92–1.14)
> 1 to ≤ 1.5 DDD	587	1.02 (0.92–1.13)
> 1.5 to ≤ 2 DDDs	200	0.96 (0.83–1.12)
> 2 DDDs	55	0.95 (0.73–1.25)
Unknown	136	0.90 (0.76–1.08)

Abbreviations: CI confidence interval, DDD defined daily dose, HR hazard ratio, NSAID nonsteroidal anti-inflammatory drug
¹Adjusted for age (time scale), years of schooling (baseline), alcohol intake (time-varying), body mass index (time-varying), physical activity level (baseline), age at menarche (baseline), parity and age at first birth (baseline), lifetime use of oral contraceptives (baseline), age at menopause (baseline), history of breast cancer in first-degree relatives (baseline), personal history of benign breast disease (time-varying), lifetime use of menopausal hormone therapy use (time-varying), and self-report of a mammogram performed during the previous follow-up cycle (time-varying). Categories used are those displayed in Table 1. HRs were obtained from separate models including one characteristic of exposure at a time
²Tests for linear trends were performed among exposed women with known characteristics of exposure. The characteristics of use were considered as continuous variables

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