Table 2.

Risk factors for the development of BM

Variable		HR	95% CI	P values
Time of initial BC diagnosis (excluding de-novo metastatic patients )
Univariate analysis
Age at BC diagnosis	>40 years	1
	≤40 years	2.61	1.29 to 5.28	0.0078
Tumour size	T1	1
	T2–4	6.68	2.34 to 19.06	0.0004
Nodal status	N0	1
	N1–3	5.00	2.16 to 11.56	0.0002
Type of surgery	BCS	1
	Mastectomy	7.86	1.84 to 33.53	0.0054
	No breast surgery	3.70	0.33 to 42.1	0.29
Multivariate analysis
Age at BC diagnosis	>40 years	1
	≤40 years	2.10	1.02 to 4.36	0.045
Tumour size	T1	1
	T2–T4	4.94	1.69 to 14.47	0.0036
Nodal status	N0	1
	N1–3	3.48	1.47 to 8.25	0.0045
Adjuvant anti-HER2 treatment	Early anti-HER2 treatment*	1
	Late anti-HER2 treatment†	2.65	1.03 to 6.82	0.043
	No anti-HER2 treatment	3.79	1.52 to 9.43	0.0042
Time of metastatic disease diagnosis (including de-novo metastatic patients)
Univariate analysis
Age at MBC diagnosis	>40 years	1
	≤40 years	2.11	1.09 to 4.10	0.028
Time from initial diagnosis to metastatic disease	<1 year	1
	≥1 year	2.18	1.15 to 4.14	0.017
Type of metastatic disease	De-novo	1
	Recurrent	1.97	1.03 to 3.75	0.0040
First metastatic site	Other than lung	1
	Lung de-novo	0.84	0.29 to 2.46	0.75
	Lung (not de-novo)	6.97	3.41 to 14.24	<0.0001
Multivariate analysis
First metastatic site	Other than lung	1
	Lung de-novo	0.84	0.29 to 2.46	0.84
	Lung (not de-novo)	6.97	3.41 to 14.24	<0.0001

*Start within the first 6 months after BC diagnosis.

†Start ≥6 months after BC diagnosis.

BC, breast cancer; BCS, breast conserving surgery; BM, brain metastases; MBC, metastatic breast cancer; N, nodal status; T, tumor size.