Table 1.

Univariate and multivariable conditional logistic regression models comparing patients developing metastatic disease with patients free from disseminating disease in a nested case–control studya

Univariate modelsMultivariable model AMultivariable model B
VariablebnHRc (95% CI)PHRc (95% CI)PHRc (95% CI)P
ACVRL1 (ALK1)1.92 (1.58–2.34)<0.0013.59 (2.51–5.15)<0.001
Endothelial metagened1.14 (0.96–1.35)0.1240.44 (0.32–0.62)<0.001
ACVRL1:endothelial metagene indexe2.17 (1.78–2.66)<0.0012.01 (1.62–2.50)<0.001
GDF2 (BMP9)1.11 (0.95–1.30)0.196
BMP101.20 (1.01–1.41)0.037
ALK1 ligands [GDF2 (BMP9) + BMP10]1.20 (1.02–1.42)0.0331.28 (1.05–1.56)0.0131.16 (0.96–1.40)0.120
SMAD61.60 (1.33–1.91)<0.0011.43 (1.15–1.77)0.0011.54 (1.26–1.89)<0.001
TGFBR1 (ALK5)1.07 (0.91–1.26)0.390
TGFB11.24 (1.05–1.47)0.012
TGFB21.03 (0.87–1.21)0.766
TGFB30.88 (0.73–1.05)0.155
Lymph node status<0.0010.0630.064
 Negative3041 (ref.)1 (ref.)1 (ref.)
 Positive4422.52 (1.69–3.77)1.72 (1.09–2.71)1.70 (1.09–2.65)
 Unknown221.11 (0.36–3.41)1.46 (0.37–5.87)1.45 (0.38–5.54)
Tumor size, mm0.0080.0320.063
 ≤203541 (ref.)1 (ref.)1 (ref.)
 >203981.73 (1.22–2.44)1.73 (1.15–2.60)1.62 (1.08–2.42)
 Unknown160.98 (0.27–3.59)1.08 (0.22–5.25)1.11 (0.24–5.12)
HER2 status<0.0010.005<0.001
 Negative5191 (ref.)1 (ref.)1 (ref.)
 Positive1452.60 (1.74–3.88)2.05 (1.28–3.30)2.36 (1.48–3.75)
 Unknown1040.75 (0.44–1.31)0.80 (0.43–1.49)0.83 (0.46–1.53)

Abbreviation: ref., reference.

  • aControls randomly matched to cases by age, adjuvant therapy, and calendar period at diagnosis.

  • bNumerical variables are centered and scaled (SD set to one) in the models. Gene-expression values are normalized log2 summarized microarray probe intensity values.

  • cFor numerical variables, HR is the relative hazard when increasing the variable one SD.

  • dAverage expression of the prototypical endothelial cell markers PECAM1, CDH5, and CD34.

  • eDifference between ACVRL1 expression and endothelial metagene expression; corresponds to (log2 of) the ratio of ACVRL1 probe intensity over average endothelial metagene probe intensity.