%0 Journal Article
%A Prat, Aleix
%A Lluch, Ana
%A Turnbull, Arran K
%A Dunbier, Anita K
%A Calvo, Lourdes
%A Albanell, Joan
%A de la Haba-Rodriguez, Juan
%A Arcusa, Angels
%A Chacon, Jose Ignacio
%A Sanchez-Rovira, Pedro
%A Plazaola, Arrate
%A Muñoz, Montserrat
%A Pare, Laia
%A Parker, Joel S
%A Ribelles, Nuria
%A Jimenez, Begoña
%A Bin Aiderus, Abdul Aziz
%A Caballero, Rosalia
%A Adamo, Barbara
%A Dowsett, Mitch
%A Carrasco, Eva
%A Martin, Miguel
%A Dixon, J Michael
%A Perou, Charles M
%A Alba, Emilio
%T A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse.
%D 2016
%U http://hdl.handle.net/10668/10654
%X 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. 
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