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Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer

2017; Impact Journals LLC; Volume: 8; Issue: 13 Linguagem: Inglês

10.18632/oncotarget.15748

1949-2553

Aranzazu Fernández-Martínez, Tomás Pascual, Giuseppe Perrone, Serafín Morales, Juan de la Haba-Rodríguez, Milagros González-Rivera, Patricia Galván, Francesca Zalfa, Michela Amato, Lucía González, Miquel Prats, Federico Rojo, Luís Manso, Laia Paré, I. Alonso, Joan Albanell, Ana Vivancos, Antonio González, Judit Matito, Sónia González, Pedro L. Fernández, Bárbara Adamo, Montserrat Muñoz, Margarita Viladot, Carme Font, Francisco Aya, María Vidal, Rosalía Caballero, Eva Carrasco, Vittorio Altomare, Giuseppe Tonini, Aleix Prat, Miguel Martín,

HER2/EGFR in Cancer Research

// Aranzazu Fernandez-Martinez 1, 2 , Tomás Pascual 1, 2 , Giuseppe Perrone 3 , Serafin Morales 4 , Juan de la Haba 5 , Milagros González-Rivera 6 , Patricia Galván 1, 2, 7 , Francesca Zalfa 3 , Michela Amato 3 , Lucia Gonzalez 8 , Miquel Prats 9 , Federico Rojo 10 , Luis Manso 11 , Laia Paré 1, 2 , Immaculada Alonso 1 , Joan Albanell 12 , Ana Vivancos 7 , Antonio González 13 , Judit Matito 7 , Sonia González 14 , Pedro Fernandez 1 , Barbara Adamo 1, 2 , Montserrat Muñoz 1, 2 , Margarita Viladot 1, 2 , Carme Font 1, 2 , Francisco Aya 1, 2 , Maria Vidal 1, 2 , Rosalía Caballero 15 , Eva Carrasco 15 , Vittorio Altomare 3 , Giuseppe Tonini 3 , Aleix Prat 1, 2, 7 , Miguel Martin 6 1 Medical Oncology Department, Hospital Clínic of Barcelona, Barcelona, Spain 2 Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain 3 Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy 4 Medical Oncology Deparment, Arnau de Vilanova de Lleida Universitary Hospital, Lleida, Spain 5 Medical Oncology Department, Reina Sofía University Hospital, Cordoba, Spain 6 Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Madrid, Spain 7 Vall d'Hebron Institute of Oncology, Barcelona, Spain 8 Medical Oncology Department, Quirón Hospital, Madrid, Spain 9 Master of Breast Pathology, University of Barcelona, Barcelona, Spain 10 Pathology Department, Fundación Jiménez Díaz Health Research Institute (IIS-FJD), Madrid, Spain 11 Medical Oncology Department, Doce de Octubre Hospital, Madrid, Spain 12 Medical Oncology Department, Hospital del Mar, Barcelona, Spain 13 Medical Oncology Department, MD Anderson Cancer Center, Madrid, Spain 14 Medical Oncology Department, Mutua de Terrassa Hospital, Barcelona, Spain 15 Spanish Breast Cancer Research Group Grupo Español de Investigación en Cáncer de Mama (GEICAM), Madrid, Spain Correspondence to: Miguel Martin, email: mmartin@geicam.org Aleix Prat, email: aprat@vhio.net Keywords: PAM50/Prosigna, breast cancer, Ki67, estrogen receptor-positive/HER2-negative Received: October 19, 2016 Accepted: January 27, 2017 Published: February 27, 2017 ABSTRACT PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however, the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0-10% group was 42.7% (with tumor sizes ≤2 cm) and 33.9% (with tumor sizes > 2 cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low-risk outcome patients or Luminal A disease in the clinical setting is unreliable. In the absence of a well-validated prognostic gene expression-based assay, the optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A disease remains at 14%.