A PAM50-based chemoendocrine score for hormone receptor-positive breast cancer with an intermediate risk of relapse

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• dc.contributor.author Prat, Aleixca
• dc.contributor.author Alba, Emilioca
• dc.contributor.author Albanell Mestres, Joan
• dc.date.accessioned 2017-12-13T08:11:28Z
• dc.date.issued 2017
• dc.description.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
• dc.format.mimetype application/pdfca
• dc.identifier.citation Prat A, Lluch A, Turnbull AK, Dunbier AK, Calvo L, Albanell . 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):3035-3044. DOI: 10.1158/1078-0432.CCR-16-2092
• dc.identifier.doi http://dx.doi.org/10.1158/1078-0432.CCR-16-2092
• dc.identifier.issn 1078-0432
• dc.identifier.uri http://hdl.handle.net/10230/33462
• dc.language.iso eng
• dc.publisher American Association for Cancer Research (AACR)ca
• dc.relation.ispartof Clinical Cancer Research. 2017 Jun 15;23(12):3035-44
• dc.rights © American Association for Cancer Research (AACR) http://dx.doi.org/10.1158/1078-0432.CCR-16-2092
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Mama -- Càncer -- Tractament
• dc.title A PAM50-based chemoendocrine score for hormone receptor-positive breast cancer with an intermediate risk of relapseca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion