Statin use as a moderator on the association between metformin and breast cancer risk in women with type 2 diabetes mellitus

Table 2 Modification of the time-varying association between metformin and breast cancer risk by statins separately after 3-, 5-, 7- and 10-years of follow up

Follow up	Crude model ^†		Model 1 ^‡		Model 2 ^§
Follow up	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
3-year
without interaction with statins with interaction with statins	0.81 [0.74, 0.88]	< 0.001	0.83 [0.76, 0.90]	< 0.001	0.82 [0.75, 0.90]	< 0.001
0	-	-	0.87 [0.79, 0.95]	0.002	0.86 [0.78, 0.94]	0.001
1	-	-	0.84 [0.77, 0.92]	< 0.001	0.84 [0.76, 0.91]	< 0.001
3	-	-	0.79 [0.73, 0.87]	< 0.001	0.79 [0.72, 0.86]	< 0.001
5	-	-	0.75 [0.68, 0.83]	< 0.001	0.74 [0.67, 0.82]	< 0.001
5-year
without interaction with statins with interaction with statins^¶	0.87 [0.83, 0.92]	< 0.001	0.88 [0.83, 0.93]	< 0.001	0.88 [0.83, 0.93]	< 0.001
0	-	-	0.97 [0.90, 1.04]	0.356	0.96 [0.89, 1.04]	0.347
1	-	-	0.94 [0.88, 1.00]	0.047	0.94 [0.88, 1.00]	0.050
3	-	-	0.88 [0.84, 0.93]	< 0.001	0.88 [0.84, 0.93]	< 0.001
5	-	-	0.83 [0.78, 0.89]	< 0.001	0.83 [0.78, 0.89]	< 0.001
7-year
without interaction with statins with interaction with statins^¶	0.90 [0.85, 0.95]	< 0.001	0.90 [0.85, 0.96]	0.001	0.91 [0.86, 0.97]	0.002
0	-	-	1.01 [0.92, 1.10]	0.900	1.01 [0.93, 1.10]	0.820
1	-	-	0.98 [0.91, 1.05]	0.517	0.98 [0.91, 1.06]	0.617
3	-	-	0.92 [0.87, 0.98]	0.005	0.93 [0.87, 0.98]	0.011
5	-	-	0.87 [0.81, 0.92]	< 0.001	0.87 [0.82, 0.93]	< 0.001
10-year
without interaction with statins with interaction with statins	0.95 [0.86, 1.05]	0.325	0.95 [0.85, 1.05]	0.283	0.96 [0.87, 1.06]	0.437
0	-	-	1.06 [0.94, 1.20]	0.329	1.08 [0.95, 1.22]	0.245
1	-	-	1.03 [0.92, 1.16]	0.588	1.05 [0.93, 1.17]	0.445
3	-	-	0.97 [0.88, 1.08]	0.588	0.99 [0.89, 1.09]	0.800
5	-	-	0.92 [0.83, 1.01]	0.086	0.93 [0.84, 1.03]	0.163

^† Crude model: include cumulative exposure to metformin and its interaction with time; ^‡ Model 1: include cumulative exposure to metformin and statins, and their interaction with time, with and without the interaction term between metformin and statins; ^§ Model 2: additionally adjust for baseline information, i.e., age, BMI, smoking status, duration of diabetes, a history of cardiovascular diseases, a history of hypertension, calendar year, as well as updated values of HbA1c, LDL-C, and eGFR, and cumulative exposure to sulfonylurea and insulin to Model 1. ^¶ Without interaction refers to without including the interaction term between metformin and statins into the model
Abbreviations: CI, confidence interval; HR, hazard ratio

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