HER2 staining intensity in HER2-positive disease: relationship with FISH amplification and clinical outcome in the HERA trial of adjuvant trastuzumab
Menée sur 425 patientes atteintes d'un cancer primitif du sein HER2+ et 850 témoins inclus dans un essai évaluant le trastuzumab en traitement adjuvant (durée médiane de suivi : 2 ans), cette étude évalue l'association entre des différences d'intensité de la coloration d'un test immunochimique ciblant la protéine HER2 et la survie sans maladie des patientes
Background : Trastuzumab treatment improves survival of HER2-positive primary breast cancer. HER2 staining intensity varies widely in HER2-positive tumours.
Patients and methods : We investigated whether differences in immunohistochemical (IHC) staining intensity for HER2 in HER2-positive tumors (IHC 3+ or FISH ratio ≥2.0) was associated with prognosis or benefit from trastuzumab treatment in patients randomized to 1 year or no trastuzumab in the HERceptin Adjuvant (HERA) trial. Median follow-up was 2 years. The nested case–control analysis, included 425 patients (cases) with a disease-free survival (DFS) event and two matched controls (no DFS event) per case. Tissue sections stained for HER2 were assessed for HER2 staining intensity by image analysis.
Results : HER2 staining intensity varied widely and correlated with HER2 gene copy number (Spearman, r = 0.498, P < 0.001) or less closely with HER2/CEP17 FISH ratio (r = 0.396, P < 0.001). We found no significant difference in DFS in the observation arm according to staining intensity (odds ratio [OR] change per 10 unit change in intensity: 1.015, 95% confidence interval [CI] 0.930–1.108) and no impact of staining intensity on benefit derived from 1-year trastuzumab (OR: 1.017, 95% CI 0.925–1.120).
Conclusions : Variability in HER2 staining in HER2-positive tumours has no role in clinical management with adjuvant trastuzumab.
Annals of Oncology , résumé, 2013