Impact of the Prosigna assay on neoadjuvant treatment decision-making in patients with early-stage HR-positive/HER2-negative breast cancer: a single-center prospective observational study

Background: The 50-gene assay Prosigna is cleared by the United States Food and Drug Administration only in postoperative hormone receptor-positive (HR-positive) breast cancer (BC) specimens. Given studies showing that Prosigna may identify chemo-sensitive tumors, this decision-impact study evaluated whether the assay could influence physicians’ choices and patients’ confidence in the neoadjuvant treatment plan. Patients and methods: This single-center prospective observational study included patients with early-stage HR-positive/HER2-negative BC measuring ≥0.5 cm, any nodal status, deemed as possible candidates for neoadjuvant treatment per physician's choice. Formalin-fixed, paraffin-embedded core biopsy specimens were centrally analyzed using Prosigna. Physicians and patients were surveyed before and after Prosigna testing. The primary endpoint was the proportion of patients whose treatment differed from the pre-Prosigna recommendation. Secondary endpoints included assessing (i) reasons for treatment changes, (ii) physicians’ and patients’ confidence in the treatment recommendation and (iii) the association of residual cancer burden (RCB) with risk of recurrence (ROR) risk groups (RG). Results: Fifty-four patients were enrolled between March 2019 and April 2023. Tumors were luminal A, luminal B, HER2-enriched and basal-like in 27.8%, 63.0%, 5.6% and 3.7% of cases, respectively. ROR RG was low, intermediate, and high in 18.5%, 20.4% and 61.1% of cases, respectively. A change in the treatment plan occurred in 35.2% of cases [95% confidence interval (CI) 23.1%-50.2%]. Among 14 questionnaires regarding reasons for treatment changes, ROR RG alone and both ROR RG and intrinsic subtype were reported in 35.7% and 64.3% of cases, respectively. Of treating physicians, 83.7% felt their confidence in the appropriateness of the treatment plan remained stable or improved, and 62.5% of patients reported reduced anxiety. No association between RCB and ROR RG was found. Conclusions: Performing Prosigna on upfront core biopsies may influence the neoadjuvant treatment decision-making in early-stage HR-positive/HER2-negative BC. ClinicalTrials.gov number, NCT03749421.