. 2023 Nov 30;21:157. doi: 10.18332/tid/174132

Table 4.

Association between cigarette smoking variables and breast cancer subtypes, 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)
	Co	HR+ (N= 1144)			HER2+ (N =300)			TN (N= 134)				Co	HR+ (N= 405)			HER2+ (N = 105)			TN (N= 49)				Co	HR+ (N= 738)			HER2+ (N = 195)			TN (N= 85)
	n	n	RRR^a	95% CI	n	RRR^a	95% CI	n	RRR^a	95% CI	p-het	n	n	RRR^b	95% CI	n	RRR^b	95% CI	n	RRR^b	95% CI	p-het	n	n	RRR^c	95% CI	n	RRR^c	95% CI	n	RRR^c	95% CI	p-het
Smoking status (1 year before the interview)
Never smoker	1142	638	1.00		173	1.00		81	1.00			237	155	1.00		46	1.00		19	1.00			904	483	1.00		127	1.00		62	1.00
Former smoker ≥10	180	122	1.05	0.79–1.41	20	0.54	0.30–0.97	9	0.49	0.21–1.17	0.028	53	44	1.42	0.86–2.34	9	1.18	0.51–2.73	2	0.75	0.16–3.53	0.680	126	78	0.84	0.56–1.25	11	0.28	0.11–0.68	7	0.42	0.12–1.47	0.040
Former smoker <10	189	109	0.91	0.67–1.24	35	1.04	0.65–1.65	11	0.43	0.18–1.05	0.207	80	59	1.21	0.78–1.88	15	1.08	0.53–2.24	5	0.62	0.17–2.26	0.596	109	50	0.71	0.43–1.15	20	0.96	0.48–1.93	6	0.42	0.09–1.93	0.531
Active smoker	390	267	1.05	0.83–1.32	71	1.00	0.69–1.44	33	0.83	0.49–1.42	0.703	175	142	1.37	0.97–1.93	35	1.26	0.72–2.19	23	1.51	0.69–3.29	0.917	213	124	0.91	0.64–1.29	36	0.64	0.35–1.15	10	0.57	0.22–1.52	0.387
p-trend				0.850			0.936			0.287					0.089			0.447			0.383					0.392			0.167			0.170
Age at smoking initiation (years)
Never smoker	1142	638	1.00		173	1.00		81	1.00			237	155	1.00		46	1.00		19	1.00			904	483	1.00		127	1.00		62	1.00
≥18	369	244	1.02	0.82–1.28	55	0.82	0.56–1.20	26	0.65	0.36–1.17	0.216	101	96	1.61	1.09–2.39	20	1.35	0.72–2.54	10	1.14	0.42–3.12	0.719	267	148	0.82	0.60–1.12	35	0.55	0.32–0.94	16	0.52	0.21–1.25	0.144
<18	389	258	1.01	0.80–1.28	72	0.96	0.66–1.10	27	0.65	0.37–1.16	0.330	209	153	1.22	0.87–1.70	39	1.11	0.65–1.92	20	1.14	0.51–2.51	0.942	178	104	0.89	0.60–1.32	33	0.65	0.34–1.23	7	0.45	0.14–1.43	0.176
p-trend				0.890			0.717			0.102					0.222			0.667			0.745					0.213			0.030			0.144
Duration of tobacco use (years)
Never smoker	1142	638	1.00		173	1.00		81	1.00			237	155	1.00		46	1.00		19	1.00			904	483	1.00		127	1.00		62	1.00
≤20	229	163	1.14	0.87–1.50	36	0.84	0.53–1.34	22	0.78	0.40–1.51	0.281	130	100	1.46	1.00–2.14	23	1.15	0.62–2.11	13	1.03	0.41–2.59	0.607	98	63	0.89	0.57–1.38	13	0.39	0.16–0.94	9	0.51	0.15–1.82	0.162
20–30	228	162	1.02	0.77–1.33	50	1.10	0.72–1.67	18	0.71	0.37–1.37	0.511	138	102	1.11	0.76–1.61	27	1.10	0.60–2.03	12	1.04	0.47–2.65	0.991	89	60	1.04	0.65–1.67	23	1.04	0.52–2.10	6	0.67	0.18–2.45	0.804
>30	299	170	0.91	0.71–1.18	40	0.77	0.50–1.19	13	0.52	0.25–1.05	0.255	40	42	1.75	1.00–3.07	9	1.81	0.73–4.47	5	2.37	0.64–8.86	0.903	258	127	0.75	0.53–1.06	31	0.52	0.29–0.93	8	0.42	0.15–1.16	0.301
p-trend				0.561			0.418			0.048					0.109			0.332			0.446					0.141			0.048			0.087
Intensity (cigarettes/day)
Never smoker	1142	638	1.00		173	1.00		81	1.00			237	155	1.00		46	1.00		19	1.00			904	483	1.00		127	1.00		62	1.00
<15	363	238	1.03	0.82–1.30	57	0.87	0.59–1.27	24	0.57	0.31–1.04	0.132	153	125	1.35	0.95–1.91	29	1.11	0.63–1.98	11	0.84	0.34–2.07	0.524	209	112	0.80	0.56–1.14	28	0.53	0.29–0.97	13	0.28	0.08–0.97	0.135
≥15	371	251	1.02	0.81–1.29	67	0.92	0.63–1.34	29	0.78	0.45–1.36	0.589	149	118	1.40	0.98–2.01	30	1.38	0.78–2.46	19	1.61	0.70–3.73	0.945	220	133	0.89	0.63–1.26	37	0.62	0.34–1.12	10	0.77	0.32–1.87	0.494
p-trend				0.827			0.600			0.249					0.058			0.273			0.316					0.395			0.054			0.320
Cumulative exposure (pack-years)
Never smoker	1142	638	1.00		173	1.00		81	1.00			237	155	1.00		46	1.00		19	1.00			904	483	1.00		127	1.00		62	1.00
<10	256	168	1.00	0.77–1.30	39	0.83	0.53–1.28	19	0.60	0.31–1.17	0.272	127	94	1.32	0.91–1.92	21	0.99	0.83–1.84	10	0.86	0.33–2.23	0.506	128	73	0.75	0.49–1.14	18	0.50	0.24–1.04	9	0.40	0.11–1.39	0.405
10–25	240	149	0.93	0.71–1.22	41	0.93	0.60–1.43	19	0.70	0.36–1.37	0.716	105	93	1.42	0.96–2.11	24	1.51	0.82–2.80	10	1.28	0.48–3.37	0.953	134	56	0.71	0.45–1.10	17	0.43	0.19–0.96	9	0.51	0.14–1.78	0.475
>25	234	164	1.11	0.85–1.46	43	0.94	0.60–1.47	15	0.74	0.38–1.44	0.408	68	51	1.31	0.81–2.12	14	1.38	0.63–3.00	10	1.83	0.62–5.43	0.835	165	113	1.06	0.73–1.54	29	0.77	0.42–1.44	5	0.66	0.23–1.87	0.458
p-trend				0.662			0.712			0.231					0.099			0.211			0.295					0.771			0.133			0.256
Years smoking before first birth^a
Never smoker	939	526	1.00		147	1.00		66	1.00			162	114	1.00		36	1.00		14	1.00			776	412	1.00		111	1.00		52	1.00
<10	253	170	1.02	0.77–1.35	40	0.69	0.43–1.11	20	0.66	0.33–1.32	0.171	87	78	1.43	0.90–2.28	19	1.05	0.49–2.23	10	1.17	0.44–3.44	0.698	165	92	0.79	0.52–1.19	21	0.34	0.16–0.75	10	0.35	0.09–1.32	0.075
≥10	260	174	1.03	0.77–1.38	38	0.82	0.50–1.34	18	0.67	0.33–1.33	0.369	132	106	1.22	0.80–1.88	20	0.93	0.44–1.96	12	1.18	0.42–3.32	0.773	127	68	0.99	0.62–1.58	18	0.67	0.31–1.48	6	0.52	0.13–1.99	0.449
p-trend				0.838			0.243			0.178					0.264			0.854			0.730					0.713			0.068			0.172
Cigarettes per day before first birth^a
Never smoker	939	526	1.00		147	1.00		66	1.00			162	114	1.00		36	1.00		14	1.00			776	412	1.00		111	1.00		52	1.00
<15	226	146	1.01	0.76–1.35	28	0.58	0.34–0.99	18	0.67	0.33–1.37	0.092	95	85	1.43	0.92–2.21	17	0.91	0.42–1.94	6	0.86	0.27–2.71	0.395	130	61	0.73	0.47–1.16	11	0.27	0.10–0.72	12	0.30	0.07–1.39	0.097
≥15	212	139	0.97	0.72–1.31	36	0.94	0.58–1.52	12	0.62	0.29–1.32	0.517	88	74	1.29	0.81–2.03	17	1.37	0.66–2.85	8	1.10	0.35–3.46	0.945	123	65	0.90	0.56–1.44	19	0.72	0.34–1.55	4	0.73	0.21–2.56	0.836
p-trend				0.878			0.491			0.163					0.229			0.464			0.925					0.442			0.117			0.368

RRR: relative risk ratio. Multinomial logistic regression analyses were used to test whether each tobacco variable was associated with specific tumor subtypes. The p-trend values were calculated by incorporating the categorized variable as a continuous variable in the multivariable models. The difference of effects of the corresponding variable between tumor subtypes was calculated as p-value of heterogeneity.

Only parous women.

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

RRR 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 hormonal contraceptive use.

RRR and 95% CI adjusted for age, education level, region, BMI, age at first birth, number of children, previous biopsies, family history of breast cancer, history of hormone replacement therapy and age at menopause. p-het: heterogeneity of effects of each tobacco variable between tumor subtypes.