Background: Prosigna is a standardized test measuring expression levels of 50 classifier genes (PAM50) in formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue using nCounter Technology (NanoString Technologies, Inc., Seattle, WA). It provides intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability. This Decision Impact study examines whether the Prosigna test influences adjuvant treatment decision beyond immunohistochemistry (IHC) testing. Methods: The analytic sample was comprised of postmenopausal early-stage breast cancer (EBC) women with estrogen-receptor positive, HER2 negative, pT1-T2 pN0/pN1mi tumors. FFPE surgical specimens were centrally analyzed using Prosigna to classify patients according to the intrinsic tumor subtype and ROR score. The primary endpoint was the effect of the Prosigna test on oncologists’ adjuvant treatment recommendations, and the actual treatment received by patients. Secondary endpoints included evaluation of tumor and patient characteristics that are associated with treatment modification. Results: A total of 205 patients met eligibility criteria and were enrolled in 8 centers between March 2015 and January 2016: 59% of tumors were classified by PAM50 as Luminal A, 39% as Luminal B, 1% Basal, .5% HER2. Clinicians, using local IHC, classified 15% of PAM50 Luminal A as Luminal B, and 40% PAM50 Luminal B as luminal A (overall 27% discordance). Prosigna results led to a reported change in chemotherapy indication in 17% overall (23% according to the French guidelines). Grade 1-2 tumors with progesterone receptor expression less than 20% or Ki67 between 10 and 20% were significantly associated with modification of adjuvant treatment (p < .001). Conclusions: In this prospective Decision Impact study, Prosigna results led to a 17% change in chemotherapy indication. The 27% discordance in intrinsic subtyping between PAM50 and IHC underlines the importance of molecular testing for optimal systemic therapy indications in EBC, particularly fot grade 1-2 tumors with progesterone receptor expression less than 20% or Ki67 between 10 and 20%. Clinical trial information: NCT02395575