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Title: A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse.
Authors: Prat, Aleix
Lluch, Ana
Turnbull, Arran K
Dunbier, Anita K
Calvo, Lourdes
Albanell, Joan
de la Haba-Rodríguez, Juan
Arcusa, Angels
Chacón, José Ignacio
Sánchez-Rovira, Pedro
Plazaola, Arrate
Muñoz, Montserrat
Paré, Laia
Parker, Joel S
Ribelles, Nuria
Jimenez, Begoña
Bin Aiderus, Abdul Aziz
Caballero, Rosalía
Adamo, Barbara
Dowsett, Mitch
Carrasco, Eva
Martín, Miguel
Dixon, J Michael
Perou, Charles M
Alba, Emilio
metadata.dc.subject.mesh: Aged
Antineoplastic Agents, Hormonal
Breast Neoplasms
Gene Expression Regulation, Neoplastic
Middle Aged
Neoadjuvant Therapy
Neoplasm Proteins
Neoplasm Recurrence, Local
Receptor, ErbB-2
Receptors, Estrogen
Receptors, Progesterone
Issue Date: 30-Nov-2016
Abstract: Purpose: 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. ©2016 AACR.
metadata.dc.identifier.doi: 10.1158/1078-0432.CCR-16-2092
Appears in Collections:Producción 2020

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