title: Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study.
abstract: There are several prognostic multigene-based tests for managing breast cancer (BC), but limited data comparing them in the same cohort. We compared the prognostic performance of the EndoPredict (EP) test (standardized for pathology laboratory) with the research-based PAM50 non-standardized qRT-PCR assay in node-positive estrogen receptor-positive (ER+) and HER2-negative (HER2-) BC patients receiving adjuvant chemotherapy followed by endocrine therapy (ET) in the GEICAM/9906 trial. EP and PAM50 risk of recurrence (ROR) scores [based on subtype (ROR-S) and on subtype and proliferation (ROR-P)] were compared in 536 ER+/HER2- patients. Scores combined with clinical information were evaluated: ROR-T (ROR-S, tumor size), ROR-PT (ROR-P, tumor size), and EPclin (EP, tumor size, nodal status). Patients were assigned to risk-categories according to prespecified cutoffs. Distant metastasis-free survival (MFS) was analyzed by Kaplan-Meier. ROR-S, ROR-P, and EP scores identified a low-risk group with a relative better outcome (10-year MFS: ROR-S 87 %; ROR-P 89 %; EP 93 %). There was no significant difference between tests. Predictors including clinical information showed superior prognostic performance compared to molecular scores alone (10-year MFS, low-risk group: ROR-T 88 %; ROR-PT 92 %; EPclin 100 %). The EPclin-based risk stratification achieved a significantly improved prediction of MFS compared to ROR-T, but not ROR-PT. All signatures added prognostic information to common clinical parameters. EPclin provided independent prognostic information beyond ROR-T and ROR-PT. ROR and EP can reliably predict risk of distant metastasis in node-positive ER+/HER2- BC patients treated with chemotherapy and ET. Addition of clinical parameters into risk scores improves their prognostic ability.
authors.affiliation: Department of Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañon, Universidad Complutente de Madrid, Calle Maiquez 7, Madrid, Spain. mmartin@geicam.org.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.affiliation: Sividon Diagnostics GmbH, Cologne, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Brase
authors.affiliation: Department of Medical Oncology, Valencian Institute of Oncology (IVO), Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Sividon Diagnostics GmbH, Cologne, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.affiliation: Department of Medical Oncology, A Coruña University Hospital Complex, A Coruña, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Calvo
authors.affiliation: Sividon Diagnostics GmbH, Cologne, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Petry
authors.affiliation: Solid Tumor Molecular Diagnostics Laboratory, ARUP Laboratories, Utah, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bernard
authors.affiliation: Department of Medical Oncology, Virgen del Rocio University Hospital, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz-Borrego
authors.affiliation: Sividon Diagnostics GmbH, Cologne, Germany.
authors.forename: Karsten E
authors.initials: KE
authors.lastname: Weber
authors.affiliation: Department of Medical Oncology, Salamanca University Hospital-IBSAL, Salamanca, Spain.
authors.forename: César A
authors.initials: CA
authors.lastname: Rodriguez
authors.affiliation: Department of Medical Oncology, Donostia University Hospital, Donostia, Spain.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Alvarez
authors.affiliation: Department of Medical Oncology, Parc Tauli University Hospital, Sabadell, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Segui
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Spanish Breast Cancer Research Group (GEICAM), Madrid, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Casas
authors.affiliation: Spanish Breast Cancer Research Group (GEICAM), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: Spanish Breast Cancer Research Group (GEICAM), Madrid, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Caballero
authors.affiliation: Department of Medical Oncology, Elche University General Hospital, Elche, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rodriguez-Lescure
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Breast cancer; Chemotherapy; EndoPredict; PAM50; Prognosis