Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.

Autor:	Cejalvo JM; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain., Martínez de Dueñas E; Hospital Provincial de Castellón, Castellón, Spain.; GEICAM, Spanish Breast Cancer Group, Madrid, Spain., Galván P; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., García-Recio S; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Burgués Gasión O; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Department of Pathology, Hospital Clínico Universitario de Valencia, Spain., Paré L; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Antolín S; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Complejo Hospitalario Universitario A Coruña, A Coruña, Spain., Martinello R; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Blancas I; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Hospital Clínico San Cecilio, Complejo Hospitalario de Granada, Granada, Spain., Adamo B; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Guerrero-Zotano Á; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Instituto Valenciano de Oncología, Valencia, Spain., Muñoz M; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Nucíforo P; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Vidal M; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Pérez RM; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Hospital Universitario Quirón de Madrid, Madrid, Spain., Chacón López-Muniz JI; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Hospital Virgen de la Salud, Toledo, Spain., Caballero R; GEICAM, Spanish Breast Cancer Group, Madrid, Spain., Peg V; Pathology Department, Hospital Vall d'Hebron, Barcelona, Spain., Carrasco E; GEICAM, Spanish Breast Cancer Group, Madrid, Spain., Rojo F; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Fundación Jiménez Díaz, Madrid, Spain.; Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain., Perou CM; University of North Carolina, Chapel Hill, North Carolina., Cortés J; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Ramón y Cajal University Hospital, Madrid, Spain., Adamo V; University of Messina, Messina, Italy., Albanell J; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Hospital del Mar, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain., Gomis RR; Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.; ICREA, Barcelona, Spain., Lluch A; GEICAM, Spanish Breast Cancer Group, Madrid, Spain.; Department of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain.; Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain., Prat A; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. alprat@clinic.cat.; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2017 May 01; Vol. 77 (9), pp. 2213-2221. Date of Electronic Publication: 2017 Mar 01.
DOI:	10.1158/0008-5472.CAN-16-2717
Abstrakt:	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 χ 2 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 . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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