Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: analysis from the phase III randomized ShortHER trial

Abstract

Abstract Background We evaluated the impact of the type of endocrine therapy on disease-free survival (DFS) in patients with HR-positive/HER2-positive BC enrolled in the phase III ShortHER trial. Methods Short-HER randomized 1254 patients with HER2-positive early BC to 9 weeks vs 1 year of adjuvant trastuzumab combined with anthracycline-taxane chemotherapy. The type of adjuvant endocrine was collected during the first 5 years of follow-up and was classified as: aromatase inhibitor (AI), tamoxifen and aromatase inhibitor (TAM-AI), or tamoxifen (TAM). The use of gonadotropin-releasing hormone analogues (GnRHa) was also collected. DFS was calculated from randomization to disease recurrence, second primary tumor, or death. Results 784 patients with HR-positive BC were included: 60.5% postmenopausal, median age 55 years. The pattern of endocrine therapy was: 59.6% AI, 23.8% TAM, 16.6% TAM-AI. At a median follow up of 8.7 years, patients who received AI had a significantly better DFS vs patients who received TAM or TAM-AI: 8-yr DFS 86.4% vs 79.7%, log-rank P = 0.013 (HR 1.52, 95%CI 1.09–2.11). In multivariate analysis, the type of endocrine therapy maintained a significant association with DFS (HR 1.64, 95% CI 1.07–2.52, p = 0.025 for TAM/TAM-AI vs AI). Among premenopausal patients aged ≤ 45 years (97% receiving TAM or TAM-AI), the use of GnRHa was associated with longer DFS: 8-yr DFS rate 85.2% vs 62.6% (log-rank p = 0.019, HR 0.41, 95% CI 0.19–0.88). Conclusions In this post-hoc analysis of the ShortHER trial adjuvant treatment with AI was independently associated with improved DFS. Subgroup analysis in young premenopausal patients suggests benefit with ovarian suppression. Trial registration: NCI ClinicalTrials.gov number: NCT00629278. Registered 5 March 2008. Retrospectively registered (first patient in December 2007).