1423PD - Molecular profiling of angiosarcomas of the breast

Date 27 September 2014
Event ESMO 2014
Session Sarcoma
Topics Soft Tissue Sarcomas
Pathology/Molecular Biology
Presenter Edibaldo Silva
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors E. Silva1, Z. Gatalica2, S. Vranic3, G. Basu2, S.K. Reddy4, A. Voss5
  • 1Department Of Surgery, University of Nebraska Medical Center, 68198-6345, - Omaha/US
  • 2Molecular Diagnostics, Caris Life Sciences, Phoenix/US
  • 3Pathology, Clinical Center, University of Sarajevo, 71000 - Sarajevo/BA
  • 4Hematology And Oncology, Los Alamitos Hematology Oncology, Los Alamitos/US
  • 5Clinical Affairs, Caris Lifesciences, Basel/CH




Angiosarcoma of the breast is a rare, aggressive soft tissue neoplasm occurring as either a primary or secondary malignancy due to previous radiotherapy for breast carcinoma. There is an unmet medical need for targeted therapies for angiosarcoma.


Seventeen patients with angiosarcoma of the breast were identified (Caris Life Sciences) and profiled for biomarkers of drug response using multiplatform methodologies (Tumor DNA sequencing, gene copy number alterations, RNA/microarray and protein/IHC expression).


Eight primary, 5 post-radiation and 4 mammary angiosarcomas of unknown etiology were identified in women (age 31-85 years), all exhibiting multiple biomarker alterations. Eight out of 17 cases (47%) harbored overexpression (mRNA and/or protein) of the genes [VEGFR2 (5/17), PDGFRA/PDGFRB (3/17), c-KIT (2/17)] that can be targeted by multikinase inhibitor Sunitinib. Based on the VEGFR2 overexpression, one patient with recurrent, refractory angiosarcoma was treated with Sunitinib resulting in a complete remission and is disease free at 14 months. Also, multiplatform molecular profiling revealed useful predictors of various other treatment modalities including anthracyclines (overexpression of topoisomerase 2α in 69%), topo 1 inhibitors (topoisomerase 1 overexpression in 44%), and fluoropyrimidines (low levels of thymidylate synthase in 29%). One case devoid of the Sunitinib-associated genetic alterations harbored a KRAS mutation indicating a potential benefit of MEK inhibitors.


A comprehensive molecular profiling of breast angiosarcomas enables identification of various molecular alterations that can be treated by both targeted and conventional treatment modalities.


All authors have declared no conflicts of interest.