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Molecular Profiling of Angiosarcomas of the Breast
Annals of Oncology 25 (Supplement 4): iv494–iv510, 2014 doi:10.1093/annonc/mdu354.12
sarcoma 1423PD
MOLECULAR PROFILING OF ANGIOSARCOMAS OF THE BREAST
abstracts
Aim: 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.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv498/2242110 by guest on 26 October 2019
E. Silva1, Z. Gatalica2, S. Vranic3, G. Basu4, S.K. Reddy5, A. Voss6 1 Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA 2 Molecular Diagnostics, Caris Life Sciences, Phoenix, AZ, USA 3 Pathology, Clinical Center, University of Sarajevo, Sarajevo, BOSNIA AND HERZEGOVINA 4 Molecular Diagnostics, Caris Life Sciences, Phoenix, AZ, USA 5 Hematology and Oncology, Los Alamitos Hematology Oncology, Los Alamitos, CA, USA 6 Clinical Affairs, Caris Lifesciences, Basel, SWITZERLAND
Methods: 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). Results: 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. Conclusions: A comprehensive molecular profiling of breast angiosarcomas enables identification of various molecular alterations that can be treated by both targeted and conventional treatment modalities. Disclosure: All authors have declared no conflicts of interest.
sarcoma 1423PD
MOLECULAR PROFILING OF ANGIOSARCOMAS OF THE BREAST
abstracts
Aim: 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.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv498/2242110 by guest on 26 October 2019
E. Silva1, Z. Gatalica2, S. Vranic3, G. Basu4, S.K. Reddy5, A. Voss6 1 Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA 2 Molecular Diagnostics, Caris Life Sciences, Phoenix, AZ, USA 3 Pathology, Clinical Center, University of Sarajevo, Sarajevo, BOSNIA AND HERZEGOVINA 4 Molecular Diagnostics, Caris Life Sciences, Phoenix, AZ, USA 5 Hematology and Oncology, Los Alamitos Hematology Oncology, Los Alamitos, CA, USA 6 Clinical Affairs, Caris Lifesciences, Basel, SWITZERLAND
Methods: 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). Results: 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. Conclusions: A comprehensive molecular profiling of breast angiosarcomas enables identification of various molecular alterations that can be treated by both targeted and conventional treatment modalities. Disclosure: All authors have declared no conflicts of interest.