Table 2. Association between cigarette smoking variables and breast cancer risk, overall and by menopausal status, multi-case-control study (MCC-Spain), 2008–2013, Spain (N=3636)

Smoking variables	All women (N=3636; Cases=1733; Controls=1903)						Pre-menopausal women (N=1157; Cases=610; Controls=547)						Post-menopausal women (N=2474; Cases=1122; Controls=1352)						p-intf
	Ca	Co	AOR b	95% CI	AOR c	95% CI	Ca	Co	AORb	95% CI	AOR d	95% CI	Ca	Co	AOR b	95% CI	AORe	95% CI
Smoking status (1 year before the interview)
Never smoker	972	1142	1.00		1.00		242	237	1.00		1.00		730	904	1.00		1.00
Former smoker ≥10	170	180	1.12	0.88–1.41	0.92	0.71–1.20	61	53	1.16	0.76–1.77	1.30	0.82–2.06	109	126	1.01	0.76–1.35	0.70	0.49–1.00
Former smoker <10	168	189	0.90	0.71–1.15	0.87	0.66–1.14	83	80	1.01	0.70–1.45	1.06	0.71–1.59	85	109	0.78	0.57–1.07	0.73	0.48–1.11
Active smoker	413	390	1.03	0.87–1.24	1.02	0.83–1.26	219	175	1.19	0.91–1.57	1.32	0.97–1.81	193	213	0.87	0.68–1.11	0.83	0.60–1.14	0.103
p–trend				0.892		0.972				0.259		0.107				0.162		0.143
Age at smoking initiation
Never smoker	972	1142	1.00		1.00		242	237	1.00		1.00		730	904	1.00		1.00
≥18	367	369	1.09	0.91–1.30	0.97	0.79–1.19	140	101	1.33	0.97–1.83	1.54	1.08–2.20	227	267	0.93	0.75–1.16	0.75	0.56–0.99
<18	389	389	0.97	0.81–1.17	0.95	0.77–1.18	227	209	1.05	0.80–1.37	1.12	0.83–1.52	161	178	0.85	0.65–1.11	0.79	0.55–1.12	0.011
p–trend				0.955		0.649				0.686		0.414				0.219		0.073
Duration of tobacco use (years)
Never smoker	972	1142	1.00		1.00		242	237	1.00		1.00		730	904	1.00		1.00
≤20	247	229	1.08	0.87–1.34	1.05	0.82–1.34	151	130	1.17	0.87–1.50	1.35	0.96–1.90	96	98	1.05	0.76–1.44	0.77	0.52–1.15
20–30	249	228	1.07	0.86–1.32	0.99	0.77–1.26	150	138	1.01	0.75–1.37	1.02	0.73–1.43	99	89	1.09	0.78–1.51	0.95	0.62–1.45
>30	251	299	0.96	0.79–1.16	0.87	0.69–1.09	61	40	1.45	0.91–2.30	1.75	1.04–2.94	189	258	0.77	0.61–0.97	0.69	0.51–0.93	0.001
p–trend				0.863		0.272				0.284		0.138				0.052		0.025
Intensity (cigarettes/day)
Never smoker	972	1142	1.00		1.00		242	237	1.00		1.00		730	904	1.00		1.00
<15	356	363	1.00	0.84–1.20	0.96	0.78–1.18	180	153	1.13	0.85–1.51	1.25	0.91–1.71	175	209	0.85	0.67–1.09	0.70	0.51–0.97
≥15	384	371	1.09	0.91–1.30	0.99	0.80–1.22	180	149	1.18	0.88–1.58	1.33	0.96–1.85	204	220	0.97	0.77–1.23	0.83	0.61–1.13	0.050
p–trend				0.378		0.876				0.244		0.075				0.655		0.129
Cumulative exposure (pack-years)
Never smoker	972	1142	1.00		1.00		242	237	1.00		1.00		730	904	1.00		1.00
<10	254	256	0.98	0.80-1.21	0.93	0.74-1.18	140	127	1.08	0.79-1.47	1.22	0.87-1.71	113	128	0.89	0.66-1.19	0.68	0.47-0.98
10-25	228	240	0.97	0.78-1.20	0.90	0.71-1.15	133	105	1.23	0.90-1.69	1.32	0.92-1.89	95	134	0.74	0.55-1.00	0.62	0.42-0.92
>25	247	234	1.16	0.94-1.42	1.06	0.83-1.35	82	68	1.15	0.78-1.68	1.32	0.85-2.04	165	165	1.05	0.81-1.36	0.98	0.70-1.37	0.059
p-trend				0.297		0.952				0.248		0.097				0.733		0.343
Years smoking before first birtha
Never smoker	801	939	1.00		1.00		177	162	1.00		1.00		624	776	1.00		1.00
<10	255	253	0.99	0.80-1.23	0.94	0.73-1.21	118	87	1.18	0.82-1.70	1.35	0.88-2.07	137	165	0.85	0.64-1.12	0.65	0.45-0.94
≥10	253	260	0.97	0.78-1.21	0.96	0.74-1.24	148	132	1.06	0.77-1.47	1.11	0.75-1.64	105	127	0.87	0.63-1.19	0.83	0.54-1.26	0.034
p-trend				0.789		0.675				0.686		0.466				0.267		0.137
Cigarettes per day before first birtha
Never smoker	801	939	1.00		1.00		177	162	1.00		1.00		624	776	1.00		1.00
<15	211	226	0.92	0.73-1.16	0.91	0.70-1.18	117	95	1.09	0.77-1.56	1.27	0.85-1.90	94	130	0.77	0.56-1.05	0.60	0.40-0.90
≥15	206	212	0.98	0.78-1.24	0.96	0.73-1.25	106	88	1.15	0.80-1.66	1.23	0.81-1.87	100	123	0.86	0.63-1.18	0.83	0.55-1.27	0.053
p-trend				0.775		0.639				0.441		0.288				0.208		0.147

AOR: adjusted odds ratio. Multivariable logistic regression analyses were used to test whether each tobacco variable was associated with breast cancer risk. The p-trend values were calculated by incorporating the categorized variable as a continuous variable in the multivariable models. The p-value of the interaction term between menopausal status and the corresponding variable was calculated using the likelihood ratio test.

^aOnly parous women.

^bOR and 95% CI adjusted for age, education level and region.

^cOR and 95% CI adjusted for age, education level, region, BMI, age at first birth, number of children, previous biopsies, family history of breast cancer, alcohol use and menopausal status.

^dOR and 95% CI adjusted for age, education level, region, age at first birth, number of children, previous biopsies, family history of breast cancer and alcohol and oral contraceptive use.

^eOR and 95% CI adjusted for age, education level, region, BMI, age at first birth, number of children, previous biopsies, family history of breast cancer, alcohol use, history of hormone replacement therapy and age at menopause.

^fp-int.: p-value of the interaction term.