Table 2.

Univariate Cox proportional hazards models of clinical factors predicting risk of bone or non-bone metastasis in patients with early-stage breast cancer

Variable	Discovery dataset (n = 960)				Validation dataset (n =335)
	Bone metastasis		Non-bone metastasis		Bone metastasis		Non-bone metastasis
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Tumor subtype*		0.0076		<0.0001		0.914		0.37
Luminal A	Ref.		Ref.		Ref.		Ref.
Luminal B	1.92 (1.08–3.39)		1.60 (0.92–2.79)		1.70 (0.34–8.43)		2.26 (0.78–6.53)
HER2+	1.56 (0.79–3.06)		2.74 (1.61–4.68)		1.08 (0.22–5.34)		1.33 (0.46–3.84)
TNBC	0.38 (0.13–1.11)		3.00 (1.81–4.97)		0.81 (0.10–6.76)		2.49 (0.92–6.73)
Pathologic stage		0.0006		<0.0001		0.0036		0.0007
I	Ref.		Ref.		—		Ref.
II	2.97 (1.60–5.50)		4.40 (2.53–7.66)		Ref.		1.87 (0.73–4.78)
III	—		—		3.71 (1.54–8.98)		5.40 (2.07–14.08)
Tumor size		0.001		<0.0001		0.0035		0.025
<2 cm	Ref.		Ref.		Ref.		Ref.
≥2 cm	2.23 (1.38–3.61)		2.07 (1.46–2.96)		4.43 (1.63–12.0)		1.99 (1.09–3.64)
Lymph node status		0.0004		<0.0001		0.0002		<0.0001
Positive	Ref.		Ref.		Ref.		Ref.
Negative	0.43 (0.27–0.69)		0.47 (0.33–0.67)		0.18 (0.07–0.45)		0.31 (0.17–0.56)
Age at diagnosis		0.1809		0.015		0.7459		0.17
≤50	Ref.		Ref.		Ref.		Ref.
>50	0.73 (0.46–1.16)		0.65 (0.46–0.92)		0.87 (0.36–2.06)		0.67 (0.37–1.19)
Nuclear grade†		0.29		0.038		0.9614		0.79
I–II	Ref.		Ref.		Ref.		Ref.
III	0.75 (0.44–1.28)		1.46 (1.02–2.08)		1.02 (0.41–2.56)		0.90 (0.46–1.77)
Endocrine therapy		0.3329		0.003		0.0667		0.50
Yes	Ref.		Ref.		Ref.		Ref.
No	1.27 (0.79–2.04)		1.80 (1.23–2.66)		0.48 (0.22–1.05)		0.82 (0.45–1.47)

Abbreviations: HR, hazard ratio; CI, confidence interval; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer.

^*Tumor subtype was determined using ER, PR, Ki67, and HER2 as defined in Materials and Methods.

^†Nuclear grade was determined by the modified Black’s method.