title: Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.
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 χ2tests 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.
authors.affiliation: 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.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Cejalvo
authors.affiliation: Hospital Provincial de Castellón, Castellón, Spain.|GEICAM, Spanish Breast Cancer Group, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez de Dueñas
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Galván
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: García-Recio
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Department of Pathology, Hospital Clínico Universitario de Valencia, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgués Gasión
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Paré
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Antolín
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: Rosella
authors.initials: R
authors.lastname: Martinello
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Hospital Clínico San Cecilio, Complejo Hospitalario de Granada, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blancas
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamo
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Guerrero-Zotano
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nucíforo
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vidal
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Hospital Universitario Quirón de Madrid, Madrid, Spain.
authors.forename: Ramón M
authors.initials: RM
authors.lastname: Pérez
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Hospital Virgen de la Salud, Toledo, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: Chacón López-Muniz
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Caballero
authors.affiliation: Pathology Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Peg
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Fundación Jiménez Díaz, Madrid, Spain.|Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Ramón y Cajal University Hospital, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.affiliation: University of Messina, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Adamo
authors.affiliation: GEICAM, Spanish Breast Cancer Group, Madrid, Spain.|Hospital del Mar, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.|ICREA, Barcelona, Spain.
authors.forename: Roger R
authors.initials: RR
authors.lastname: Gomis
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: 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.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D004967:Estrogens / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human