Article révisé par les pairs
Résumé : Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer. Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N ¼ 561) and observation (N ¼ 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest. Results: A significant interaction was detected between p27 and treatment (adjusted P ¼ 0.0049). Trastuzumab effect was significant in the p27-low subgroup (70% p27-positive tumor cells; N ¼ 318). HRComb Trast vs.Obs 0.44, 95% CI, 0.29–0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N ¼ 435; HRComb Trast vs.Obs 0.97, 95% CI, 0.66–1.44, P ¼ 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HRp27 High vs.Low 0.49, 95% CI, 0.32–0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit. Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not.

Documents en relation

DI-fusion