Artigo

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

Autor(es): Giuseppe Di Graziaa,b , Vincenzo Di Lauroc , Daniel Morch´ on-Araujod,e , Sabrina Nuceraf , Luis Figuero-P´ erezd,e, Francisco Javier Calleja-Holgadog , David Pelegrina S´anchezg, Benjamin Wallbaumh, Pablo Rivera Vargasi, Michela Palleschij , Antonino Musolinoj , Gast´ on Zatta Cobosk, Assumpci´ o L´ opez Paradísk,l, Gimena Barrosom , Ona Cano Canon, Elsa Dalmau Portulasn, Aldo Caltavituroo,p , Giuseppe Buonoc , Yolanda Jerez Gillaranzq, Isabel Echavarríaq , Sara L´ opez-Tarruellaq,r , Milana Bergamino Sirv´ena,s, Olga Martínez-S´ aeza,s,t , Barbara Adamoa,s,t, Montserrat Mu˜noz Mateua,s,t, Grazia Arpinoo,u , Rodrigo S´ anchez Bayonag, Michelino De Laurentiisc, C´ esar A. Rodríguezd,e, Tom´ as Pascuala,s,t , María Vidal Losadaa,s,t,1, Francesco Schettinia,s,t,*,

ABSTRACT
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