Kalinsky, KevinBarlow, William EGralow, Julie RMeric-Bernstam, FundaAlbain, Kathy SHayes, Daniel FLin, Nancy UPerez, Edith AGoldstein, Lori JChia, Stephen K LDhesy-Thind, SukhbinderRastogi, PriyaAlba, EmilioDelaloge, SuzetteMartin, MiguelKelly, Catherine MRuiz-Borrego, ManuelGil-Gil, MiguelArce-Salinas, Claudia HBrain, Etienne G CLee, Eun-SookPierga, Jean-YvesBermejo, BegoñaRamos-Vazquez, ManuelJung, Kyung-HaeFerrero, Jean-MarcSchott, Anne FShak, StevenSharma, PriyankaLew, Danika LMiao, JielingTripathy, DebasishPusztai, LajosHortobagyi, Gabriel N2025-01-072025-01-072021-12-16Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021 Dec 16;385(25):2336-2347https://hdl.handle.net/10668/27721The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear. In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival. A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased. Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).enAntineoplastic Agents, HormonalDisease-Free SurvivalLymphatic MetastasisPremenopauseReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleGene Expression ProfilingHumansMiddle AgedNeoplasm Recurrence, LocalPremenopauseProspective StudiesReceptors, Steroidresearch article34914339Restricted AccessRecurrenciaQuimioterapiaTerapéuticaSupervivencia sin enfermedadNeoplasias de la mamaQuimioterapia adyuvanteGanglios linfáticosNeoplasiasPronósticoGenes10.1056/NEJMoa21088731533-4406PMC9096864https://www.nejm.org/doi/pdf/10.1056/NEJMoa2108873?articleTools=truehttps://pmc.ncbi.nlm.nih.gov/articles/PMC9096864/pdf