Clinical outcomes in relation to biomarkers

In the general population, the mean follow-up was 55.7 months (range, 5–119), and relapse occurred in 106 patients (16.8%). Only 18 of these (2.8%) bore a triple-negative phenotype, representing 21.2% of this subgroup, and the remaining 88 (83%) belonged to the non-TNBC subgroup, representing 16.1% of this conventional subpopulation (P=0.246). Relapse was directly and significantly correlated with the clinical stage, grade (G), pN (P<0.001), multicentric/multifocal aspect (MC/MF; P=0.022), capsular effraction (P=0.017), in situ component (P=0.024), Ki67 (P=0.051), and CK5/6 (P=0.041), and was predicted by MC/MF, G, and CK5/6. The mean estimated EFS was 99.6 months (95% CI: 96.27–102.98), with 100.4 months (95% CI: 96.83–103.95) in non-TNBC patients vs 85.52 months (95% CI: 76.75–94.29) in TNBC patients (HR =0.732; 95% CI: 0.441–1.216; P=0.228) (Figure 1).


In TNBC patients, relapse was significantly correlated with menopausal status (P=0.016), Charlson index (P=0.065), BMI (P=0.002), pN (P=0.004), capsular effraction (P=0.024), and CK5/6 expression (P=0.006). The estimated mean for EFS in CK5/6-negative patients (68.84 months [95% CI: 50.06–87.63]) was significantly lower than that for CK5/6-positive patients (98.84 months [95% CI: 87.99–109.69]) (HR =5.075; 95% CI: 1.09–23.53; P=0.038; Figure 3). The log-rank tests for the differences between EFS and patients expressing vs those not expressing each of the other analyzed biomarkers were nonsignificant (Figure 3).

Significant differences (P=0.006) between biomarker expression in relapsed vs non-relapsed TNBC patients were found only for CK5/6-negative (42.9% [9] vs 57.1% [12]) and CK5/6-positive (8% [2] vs 92% [23]) biomarkers. Within the relapsed population, patients were primarily CK5/6 negative (81.8%), with a small CK5/6-positive group (18.2%). Based on the CK5/6-related survival outcomes and CK5/6–E-cad correlation, a score build on CK5/6 and E-cad expression was applied, namely both CK5/6 negative and E-cad negative, either CK5/6 or E-cad negative and the counterpart biomarker positive, and CK5/6 positive and E-cad positive.

The estimated EFS in the group expressing none of the biomarkers was 39.64 months (95% CI: 33.0–46.24) (HR =2.09; 95% CI: 0.38–11.47; P=0.397), 64.23 months in the group expressing either CK5/6 or E-cad (95% CI: 50.50–77.96) (HR =1.35; 95% CI: 0.25–7.37; P=0.732), and 83.87 months in the group expressing both biomarkers (95% CI: 64.24–103.51; P=0.667) (Figure 4).