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

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Date
2017-06
ICR Author
Dowsett, Mitch
Marsden,
Author
Prat, A
Lluch, A
Turnbull, AK
Dunbier, AK
Calvo, L
Albanell, J
de la Haba-Rodríguez, J
Arcusa, A
Chacón, JI
Sánchez-Rovira, P
Plazaola, A
Muñoz, M
Paré, L
Parker, JS
Ribelles, N
Jimenez, B
Bin Aiderus, AA
Caballero, R
Adamo, B
Dowsett, M
Carrasco, E
Martín, M
Dixon, JM
Perou, CM
Alba, E
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Type
Journal Article
Metadata
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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 .
URI
https://repository.icr.ac.uk/handle/internal/724
DOI
https://doi.org/10.1158/1078-0432.ccr-16-2092
Collections
  • Breast Cancer Research
  • Molecular Pathology
Subject
Humans
Breast Neoplasms
Neoplasm Recurrence, Local
Recurrence
Receptor, erbB-2
Neoplasm Proteins
Receptors, Estrogen
Receptors, Progesterone
Antineoplastic Agents, Hormonal
Prognosis
Neoadjuvant Therapy
Gene Expression Regulation, Neoplastic
Aged
Middle Aged
Female
Research team
Endocrinology
Language
eng
Date accepted
2016-11-07
License start date
2017-06
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2017, 23 (12), pp. 3035 - 3044

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