Table 3 Cox multivariate regression analysis for breast cancer survival according to CpG methylation profile, clinical factors, or intrinsic subtypes

Methylation cluster (n =517)

4 (luminal-enriched) (n =187) (reference)

1.00

-

1.00

-

1 (mixed) (n =123)

1.11

0.66-1.86

0.70

1.09

0.61-1.95

0.78

2 (basal-enriched) (n =108)

1.91

1.19-3.08

0.0075

1.41

0.76-2.64

0.28

3 (luminal-enriched) (n =99)

1.71

1.04-2.79

0.033

1.27

0.75-2.17

0.37

Clinical factor (n =517)

Age at diagnosis (continuous)

0.97

0.96-0.99

0.004

0.99

0.96-1.01

0.38

Premenopausal (versus post)

1.76

1.20-2.57

0.004

1.27

0.72-2.22

0.41

African-American (versus white/other)

1.65

1.15-2.35

0.006

1.60

1.08-2.39

0.02

HR^- (versus HR⁺)

1.58

1.09-2.30

0.02

1.07

0.65-1.76

0.80

HER2⁺ (versus HER2^-)

1.32

0.89-1.96

0.16

-

-

-

Stage (1, 2, 3, 4)

2.76

2.22-3.43

<0.0001

1.74

1.22-2.49

0.002

Grade 2/3 (versus 1)

2.51

1.46-4.31

0.0009

1.21

0.66-2.22

0.54

Lymph node-positive (versus negative)

5.25

3.44-8.00

<0.0001

3.40

2.03-5.71

<0.0001

Tumor size 2-5 cm (versus ≤2 cm)

2.32

1.52-3.55

0.0001

1.24

0.77-1.99

0.38

Tumor size >5 cm (versus ≤2 cm)

5.01

2.91-8.63

<0.0001

1.44

0.73-2.83

0.28

Intrinsic subtype (n =393) ^b

Luminal A (n =212) (reference)

1.00

-

1.00

-

Luminal B (n =65)

1.14

0.62-2.09

0.68

0.97

0.51-1.84

0.93

Basal-like (n =86)

1.49

0.88-2.50

0.13

1.10

0.63-1.91

0.74

HER2⁺/HR^- (n =26)

2.41

1.24-4.70

0.01

1.06

0.48-2.34

0.88

Unclassified (n =24)

1.34

0.57-3.17

0.50

1.19

0.49-2.87

0.70