Background: Optimal adjuvant endocrine therapy for HER2+/HR+ patients treated with chemotherapy and trastuzumab is still unclear. We evaluated the impact of the type of endocrine therapy on DFS in patients with HER2+/HR+ breast cancer enrolled in the phase III ShortHER trial. Methods: The Short-HER study randomized 1254 patients with HER2+ early breast cancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with anthracycline-taxane chemotherapy. The type of adjuvant endocrine was collected every 6 months during the first 5 years of follow-up and was classified as: aromatase inhibitor (AI), tamoxifen and aromatase inhibitor (TAM-AI, in case of both drugs were administered for at least 1 year each), or tamoxifen (TAM). For premenopausal patients, the use of GnRH analogue was also collected. DFS was calculated from randomization to disease recurrence (locoregional or metastatic), second primary invasive cancer, or death. Results: 853 patients with HR+ BC (ER and/or PgR >10%) were included: 60% postmenopausal, 40% premenopausal. The pattern of endocrine therapy was: 55% AI, 22% TAM, 15% TAM-AI (8% missing data). Among premenopausal patients, 51% received GnRH. At a median follow up of 8.7 years (IQR 7.6-9.0), patients who received AI had a significantly better DFS as compared to patients who received TAM or TAM-AI: 7-yr DFS 87.3% vs 81.7%, log-rank P=0.017 (HR 1.46, 95%CI 1.05-2.03). In multivariate analysis including menopausal status, stage, and treatment arm, the type of endocrine therapy maintained a significant association with DFS (Table). In the subgroup of premenopausal patients, the use of GnRH was associated with numerically improved DFS: 86.6% vs 81.6%, log-rank P=0.168 (HR=0.70, 95%CI 0.43-1.16). Conclusions: In this post-hoc analysis of the ShortHER trial, adjuvant treatment with aromatase inhibitor was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests potential benefit with ovarian suppression. Clinical trial information: NCT00629278.