Association between the HER2 Ile655Val Polymorphism and Response to Trastuzumab in Women with Operable Primary Breast Cancer
Menée auprès de 4 167 patientes atteintes d'un cancer primitif du sein HER2+ (1 191 cas) ou HER2- (durée médiane de suivi : 44 mois), cette étude évalue l'association entre la présence du polymorphisme Ile655Val du gène HER2 et la réponse au trastuzumab
Background : HER2 Ile655Val polymorphism may affect the efficacy of trastuzumab treatment for breast cancer.
Methods : HER2 Ile655Val polymorphism was determined in 4167 patients with primary breast cancer using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2- negative breast cancer, and in women with HER2- positive breast cancer who received trastuzumab or who did not.
Results : At a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival in either the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS )and distant disease-free survival (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.3; P=0.037; DDFS, adjusted HR, 1.9; 95%CI, 1.2-2.9 P=0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than patients with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P=0.008; 5-year DDFS, 100% versus 89%; P=0.031).
Conclusions : HER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2 positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.
Annals of Oncology , résumé, 2014