Prat, AleixLluch, AnaTurnbull, Arran KDunbier, Anita KCalvo, LourdesAlbanell, Joande la Haba-Rodriguez, JuanArcusa, AngelsChacon, Jose IgnacioSanchez-Rovira, PedroPlazaola, ArrateMuñoz, MontserratPare, LaiaParker, Joel SRibelles, NuriaJimenez, BegoñaBin Aiderus, Abdul AzizCaballero, RosaliaAdamo, BarbaraDowsett, MitchCarrasco, EvaMartin, MiguelDixon, J MichaelPerou, Charles MAlba, Emilio2023-01-252023-01-252016-11-07Prat A, Lluch A, Turnbull AK, Dunbier AK, Calvo L, Albanell J, et al. A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse. Clin Cancer Res. 2017 Jun 15;23(12):3035-3044http://hdl.handle.net/10668/10654Purpose: Hormone receptor-positive (HR+) breast cancer is clinically and biologically heterogeneous, and subgroups with different prognostic and treatment sensitivities need to be identified.Experimental Design: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2- disease randomly assigned to neoadjuvant multiagent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based chemoendocrine score (CES). CES's predictive ability was evaluated in 4 independent neoadjuvant data sets (n = 675) and 4 adjuvant data sets (n = 1,505). The association of CES, intrinsic biology, and PAM50 risk of relapse (ROR) was explored across 6,007 tumors.Results: Most genes associated with endocrine sensitivity were also found associated with chemotherapy resistance. In the chemotherapy test/validation data sets, CES was independently associated with pathologic complete response (pCR), even after adjusting for intrinsic subtype. pCR rates of the CES endocrine-sensitive (CES-E), uncertain (CES-U), and chemotherapy-sensitive (CES-C) groups in both data sets combined were 25%, 11%, and 2%, respectively. In the endocrine test/validation data sets, CES was independently associated with response. Compared with ROR, >90% of ROR-low and ROR-high tumors were identified as CES-E and CES-C, respectively; however, each CES group represented >25% of ROR-intermediate disease. In terms of survival outcome, CES-C was associated with poor relapse-free survival in patients with ROR-intermediate disease treated with either adjuvant endocrine therapy only or no adjuvant systemic therapy, but not in patients treated with (neo)adjuvant chemotherapy.Conclusions: CES is a genomic signature capable of estimating chemoendocrine sensitivity in HR+ breast cancer beyond intrinsic subtype and risk of relapse. Clin Cancer Res; 23(12); 3035-44.enAgedAntineoplastic agents, hormonalBreast neoplasmsFemaleGene expression regulation, neoplasticHumansMiddle agedNeoadjuvant therapyNeoplasm proteinsNeoplasm recurrence, localPrognosisReceptor, ErbB-2Receptors, estrogenReceptors, progesteroneRecurrenceResearch article27903675open accessAntineoplásicos hormonalesNeoplasias de la mamaPronósticoProteínas de neoplasiasReceptores de estrógenosReceptores de progesteronaRecurrencia local de neoplasia10.1158/1078-0432.CCR-16-20921557-3265PMC5449267https://cdr.lib.unc.edu/downloads/xk81jr150https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449267/pdf