Association between chemotherapy use and prognosis in young patients with stage I-II ER+ /HER2-negative breast cancer according to Prosigna®: An international real-world analysis with propensity-score matching

Background Genomic assays (GA) guide chemotherapy (CT) use in stage I-II endocrine receptor-positive (ER+)/HER2-negative (HER2-) breast cancer (BC). In tumors N0/intermediate-risk or N1/low-to-intermediate-risk, randomized trials with OncotypeDX® showed a CT benefit only for women aged≤ 50 years/premenopausal. Comparable data for the Prosigna® GA are lacking. Methods We retrospectively included 567 women aged≤ 50 years with stage I-II ER+ /HER2 − BC tested with Prosigna® across 10 hospitals in Spain/Italy (2014–2023). Patients received endocrine therapy (ET) with/without (neo)adjuvant CT. Event-free survival (EFS) was analyzed using Kaplan-Meier curves, log-rank tests, and Cox regression. Propensity score matching (PSM) was applied. 5-year EFS rates were numerically compared with those of OncotypeDX® trials. Results Of 567 patients, 73.7% were N0 and 26.3% N1, 39.7% were Prosigna risk-of-relapse (ROR)-low (RL), 33.0% ROR-intermediate (RI), 27.3% ROR-high (RH) and 48.3% received CT. CT independently improved EFS in N0/RI and N1/RL-RI (5-year EFS 97.9% vs. 86.6%; adjusted hazard ratio=0.07, p = 0.018). In premenopausal women, CT benefit persisted only when adjuvant gonadotropin-releasing hormone analogue was not administered (p = 0.008), especially in N0/RI (p = 0.023). Results were confirmed after PSM. CT-treated N0/RH showed similar EFS to CT-treated N0/RI+N1/RL-RI, while N1/RH showed poor prognosis despite CT use. 5-year EFS rates were generally consistent with OncotypeDX® trials. Conclusion Prosigna can help identify young women with stage I-II ER+ /HER2- BC who gain benefit from (neo)adjuvant CT and those in need of further escalated treatments. In premenopausal N0/RI and N1/RL-RI disease, the effect of CT seems to be driven by ovarian function suppression. Prospective validation is required.