Figure 4

Endo180 improves the prediction of metastatic BCa in the bisphosphonate-naive setting. (A) Stratification of all patients for which the index test and reference standard test were performed (n=86^a) according to low or high CA 15-3 antigen and Endo180 status with respective cutoffs of 28 U ml⁻¹ and relative plasma level of 1.15 indicated with grey arrowheads. Disease status for each patient is indicated using the following colour code: early BCa (pink), locoregional disease (yellow), visceral metastasis alone (purple), bone metastasis alone (green) and bone plus visceral metastasis (orange). The sensitivity (% true positives) and specificity (% false negatives) of Endo180 and CA 15-3 antigen for classification of metastasis are indicated as fractional numbers of patients and corresponding percentages. Patients currently (*) or previously (+) receiving bisphosphonate treatment are indicated. Box and whiskers plots depicting the total range, interquartile distribution, outliers (open and closed circles) and median value (horizontal line) of: (B) Endo180 and CA 15-3 antigen; in the 42 patients with bone metastasis with or without visceral tissue metastasis classified as bisphosphonate naive (n=13), having previously received bisphosphonates (n=5) or currently being treated with bisphosphonates (n=24). The P-values shown were determined using Kruskal–Wallis one-way ANOVA, and confirmed by Bonferroni adjustment (P=0.05/n, n=3). (C) Evaluation of the sensitivity (% true positives) and specificity (% false negatives) of Endo180 and CA 15-3 antigen in all 57 bisphosphonate-naive patients was conducted using the same criteria as used in (A). The Endo180 cutoff (1.15) chosen for the analyses presented in (A, C) was close to the Q₁ value for recurrent/metastatic BCa (1.13) and the Q₃ value for early BCa (1.13) and was higher than the upper 95% CI for early BCa (1.06). ^aData for CA 15-3 antigen were missing for 2 out of the 29 early BCa patients included in the study.