Associations of aspirin and other anti-inflammatory medications with breast cancer risk by the status of COX-2 expression

Yaghjyan, Lusine; Eliassen, A. Heather; Colditz, Graham; Rosner, Bernard; Schedin, Pepper; Wijayabahu, Akemi; Tamimi, Rulla M.

doi:10.1186/s13058-022-01575-3

Table 1 Associations of aspirin with breast cancer risk, by COX2 status defined using median, combined staining with Cayman and Thermo Scientific antibodies

From: Associations of aspirin and other anti-inflammatory medications with breast cancer risk by the status of COX-2 expression

Intake category	COX2 negative^a		COX2 positive^a		p-heterogeneity
Intake category	N	Full models, OR and 95% CI	N	Full models, OR and 95% CI	p-heterogeneity
Aspirin use
Regular use (≥ 2 times/week)
Nonusers	50/1102	Ref	102/1102	Ref
Past users	56/946	0.98 (0.63, 1.52)	60/946	1.18 (0.82, 1.70)
Current users
< 5 years	13/228	1.21 (0.64, 2.30)	15/228	0.76 (0.43, 1.35)
≥ 5 years	75/890	1.39 (0.89, 2.17)	50/890	1.32 (0.88, 2.00)
p-trend		0.06		0.42	0.41
Frequency of use
Nonusers	50/1038	Ref	102/1038	Ref
Past users	69/1057	1.00 (0.66, 1.52)	62/1057	1.06 (0.74, 1.52)
Current users
1 day/week	34/277	1.72 (1.04, 2.85)	8/277	0.55 (0.26, 1.17)
2–3 days/week	17/206	1.20 (0.65, 2.20)	19/206	1.57 (0.91, 2.71)
4–5 days/week	9/159	0.95 (0.44, 2.04)	11/159	1.47 (0.74, 2.90)
6+ days/week	43/598	1.26 (0.78, 2.03)	31/598	1.05 (0.66, 1.67)
p-trend		0.92		0.73	0.74
Dosage (number of tablets per week)
Nonusers	52/798	Ref	76/798	Ref
Past users
< 2	29/437	1.01 (0.59, 1.73)	20/437	0.94 (0.51, 1.74)
2–5	9/164	0.73 (0.32, 1.66)	6/164	1.12 (0.48, 2.62)
> 5	4/84	0.35 (0.08, 1.50)	2/84	1.29 (0.43, 3.86)
p-trend		0.11		0.77	0.15
Current users
< 2	25/350	1.30 (0.77, 2.19)	17/350	0.54 (0.29, 1.03)
2–5	22/330	1.08 (0.60, 1.94)	16/330	1.07 (0.58, 1.96)
> 5	33/343	1.71 (1.01, 2.88)	30/343	1.56 (0.95, 2.57)
p-trend		0.04		0.07	0.90
Duration (years of use by status)
Nonusers	50/1102	Ref	102/1102	Ref
Past users
< 2	0/23	< 0.00 (< 0.00, > 999.99)	2/23	1.54 (0.34, 6.87)
2–5	23/355	1.17 (0.69, 1.99)	29/355	1.07 (0.69, 1.66)
> 5	33/568	0.87 (0.52, 1.46)	29/568	1.37 (0.84, 2.24)
p-trend		0.67		0.57	0.47
Current users
< 2	7/105	1.56 (0.68, 3.58)	5/105	0.54 (0.21, 1.37)
2–5	8/146	1.11 (0.51, 2.42)	12/146	0.93 (0.49, 1.77)
> 5	73/867	1.33 (0.85, 2.08)	48/867	1.42 (0.93, 2.16)
p-trend		0.28		0.18	0.86
NSAIDs
Regular use (≥ 2 times/week)
Nonusers	85/1177	Ref	61/1177	Ref
Past users	53/856	0.94 (0.65, 1.35)	71/856	1.20 (0.83, 1.73)
Current users
< 5 years	52/605	1.09 (0.75, 1.58)	30/605	0.79 (0.50, 1.25)
≥ 5 years	34/788	0.72 (0.47, 1.11)	70/788	1.10 (0.75, 1.61)
p-trend		0.31		0.94	0.48
Frequency of use
Nonusers	85/1092	Ref	61/1092	Ref
Past users	53/851	0.89 (0.62, 1.29)	71/851	1.03 (0.71, 1.49)
Current users
1 day/week	28/427	0.80 (0.50, 1.27)	31/427	0.81 (0.51, 1.29)
2–3 days/week	23/404	0.82 (0.50, 1.35)	43/404	1.09 (0.71, 1.68)
4–5 days/week	10/116	1.28 (0.63, 2.59)	11/116	1.00 (0.50, 2.00)
6+ days/week	19/258	1.02 (0.59, 1.74)	13/258	0.80 (0.42, 1.51)
p-trend		0.80		0.93	0.81

Adjusted for age (continuous), BMI (continuous), percent breast density ((< 10%, 10 to < 25%, 25 to < 50%, ≥ 50%), age at menarche (< 12, 12, 13, > 13), a family history of breast cancer (Yes/No), a history of benign breast disease (Yes/No), NHS cohort (NHSI, NHSII), alcohol use (none, > 0 to < 5, ≥ 5 g/day), menopausal status/postmenopausal hormone use (premenopausal, postmenopausal/no hormones, postmenopausal/past hormones, postmenopausal/current hormones, postmenopausal/past/unknown current), and parity and age at first child’s birth (nulliparous, parous with age at first birth < 25, parous with age at first birth ≥ 25)
^aPositive versus negative COX-2 status was defined using the median % of positive staining for at least one of the two antibodies (Cayman Chemical or Thermo Fisher Scientific)

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