Journal Article
. 2016 Dec;23(12).
doi: 10.1158/1078-0432.CCR-16-2092.

A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse

Aleix Prat 1 Ana Lluch 2 Arran K Turnbull 3 Anita K Dunbier 4 Lourdes Calvo 5 Joan Albanell 6 Juan de la Haba-Rodríguez 7 Angels Arcusa 8 José Ignacio Chacón 9 Pedro Sánchez-Rovira 10 Arrate Plazaola 11 Montserrat Muñoz 12 Laia Paré 13 Joel S Parker 14 Nuria Ribelles 15 Begoña Jimenez 15 Abdul Aziz Bin Aiderus 3 Rosalía Caballero 16 Barbara Adamo 12 Mitch Dowsett 17 Eva Carrasco 16 Miguel Martín 18 J Michael Dixon 3 Charles M Perou 14 Emilio Alba 15 
Affiliations
  • PMID: 27903675
  •     41 References
  •     9 citations

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.

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