title: Antiangiogenic therapy in recurrent breast cancer with lymphangitic spread to the chest wall: A randomized phase II trial of bevacizumab with sequential or concurrent oral vinorelbine and capecitabine.
abstract: OBJECTIVE
  To assess efficacy of bevacizumab in combination with oral chemotherapy in patients with breast cancer with lymphangitic spread to the chest wall (LBC). To identify surrogate biomarkers of response to bevacizumab.
  
  
  METHODS
  We randomly assigned patients to receive bevacizumab plus either sequential or concurrent oral vinorelbine and capecitabine every 3 weeks. The primary endpoint was time to ultimate progression (TTP); the response rate and overall survival (OS) were secondary endpoints. We performed gene expression profiling on baseline tissue samples collected from triple negative LBC. We assessed circulating endothelial cells (CEC), circulating endothelial progenitors (CEP) and circulating pericyte progenitors (CPP).
  
  
  RESULTS
  A total of 66 patients were enrolled. There was no difference in TTP (median TTP 5.3 vs. 4.8 months, p = 0.21) and in OS (median OS 15.8 vs 11.9 months; p = 0.25) when comparing concurrent vs sequential treatment, respectively. Response rate was 25% vs 28% in the concurrent vs sequential arm (p = 1.00), respectively. A set of 16 genes predictive of response to bevacizumab was identified. The counts of CEPs and viable CECs below the median value were associated with an improved overall survival: 26.6 vs 9.5 months for CEPs and 22.6 vs 11.0 months for viable CECs, respectively (p = 0.02).
  
  
  CONCLUSIONS
  Oral chemotherapy and bevacizumab (BEVIX) is an active regimen in patients with LBC. We support the importance of using LBC as a biological model for investigating angiogenesis inhibitors. CECs and CEPs biomarkers have been identified as predictive markers of outcome and warrant further investigation.
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy. Electronic address: giuseppe.curigliano@ieo.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Division of Epidemiology and Biostatistics, Istituto Europeo di Oncologia, Italy; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: Laboratory Division of Hematology-Oncology, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.affiliation: Department of Experimental Oncology, Italy; University of Milano, School of Medicine, Milano, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Alcalay
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy.
authors.forename: Marzia Adelia
authors.initials: MA
authors.lastname: Locatelli
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Fumagalli
authors.affiliation: Laboratory Division of Hematology-Oncology, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rabascio
authors.affiliation: Laboratory Division of Hematology-Oncology, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Adamoli
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Criscitiello
authors.affiliation: Department of Pathology, Istituto Europeo di Oncologia, Italy; University of Milano, School of Medicine, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Division of Experimental Therapeutics, Breast Health Program, Istituto Europeo di Oncologia, Italy.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D000069287:Capecitabine / Q000008:administration & dosage; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D020286:Pericytes / Q000187:drug effects; D016019:Survival Analysis; D013899:Thoracic Neoplasms / Q000556:secondary*; D035441:Thoracic Wall; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D014747:Vinblastine; D000069287:Capecitabine; D000077235:Vinorelbine
keywords: Bevacizumab; Lymphangitic breast cancer; Oral chemotherapy