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Title: Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.
Authors: Cejalvo, Juan M
Martínez de Dueñas, Eduardo
Galván, Patricia
García-Recio, Susana
Burgués Gasión, Octavio
Paré, Laia
Antolín, Silvia
Martinello, Rosella
Blancas, Isabel
Adamo, Barbara
Guerrero-Zotano, Ángel
Muñoz, Montserrat
Nucíforo, Paolo
Vidal, María
Pérez, Ramón M
Chacón López-Muniz, José I
Caballero, Rosalía
Peg, Vicente
Carrasco, Eva
Rojo, Federico
Perou, Charles M
Cortés, Javier
Adamo, Vincenzo
Albanell, Joan
Gomis, Roger R
Lluch, Ana
Prat, Aleix
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Biomarkers, Tumor
Breast Neoplasms
Gene Expression Regulation, Neoplastic
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Receptor, ErbB-2
Issue Date: 1-Mar-2017
Abstract: Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 2213-21. ©2017 AACR.
metadata.dc.identifier.doi: 10.1158/0008-5472.CAN-16-2717
Appears in Collections:Producción 2020

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