title: Predictive value of angiogenesis-related gene profiling in patients with HER2-negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel.
abstract: Bevacizumab plus weekly paclitaxel improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), but its use has been questioned due to the absence of a predictive biomarker, lack of benefit in overall survival (OS) and increased toxicity. We examined the baseline tumor angiogenic-related gene expression of 60 patients with mBC with the aim of finding a signature that predicts benefit from this drug.Multivariate analysis by Lasso-penalized Cox regression generated two predictive models: one, named G-model, including 11 genes, and the other one, named GC-model, including 13 genes plus 5 clinical covariates. Both models identified patients with improved PFS (HR (Hazard Ratio) 2.57 and 4.04, respectively) and OS (HR 3.29 and 3.43, respectively). The G-model distinguished low and high risk patients in the first 6 months, whereas the GC-model maintained significance over time.
authors.affiliation: Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Mendiola
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Martínez-Marin
authors.affiliation: IMDEA, Campus de Excelencia Internacional CEI (UAM-CSIC), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Herranz
authors.affiliation: Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Heredia
authors.affiliation: Department of Pathology, La Paz University Hospital, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Yébenes
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Zamora
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castelo
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pinto
authors.affiliation: Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Miguel
authors.affiliation: Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Díaz
authors.affiliation: Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gámez
authors.affiliation: Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Juan Ángel
authors.initials: JÁ
authors.lastname: Fresno
authors.affiliation: IMDEA, Campus de Excelencia Internacional CEI (UAM-CSIC), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramírez de Molina
authors.affiliation: Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.|Department of Pathology, La Paz University Hospital, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hardisson
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Espinosa
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.|Translational Oncology Group, La Paz University Hospital - IdiPAZ, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Redondo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: angiogenesis; bevacizumab and weekly paclitaxel; gene expression; metastatic breast carcinoma; predictive