335P - Biomarkers of targeted therapies in malignant phyllodes tumors of the breast

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Locally Advanced
Translational Research
Presenter Zoran Gatalica
Citation Annals of Oncology (2014) 25 (suppl_4): iv110-iv115. 10.1093/annonc/mdu328
Authors Z. Gatalica1, G. Basu1, A. Ghazalpour1, R. Bender1, S. Vranic2, S. Millis1, J. McGill3, A. Voss4
  • 1Molecular Diagnostics, Caris Life Sciences, 85040 - Phoenix/US
  • 2Pathology, Institute of Oncology Clinical Centre of Sarajevo University, 71000 - Sarajevo/BA
  • 3Cytogenetics, Miraca Life Sciences, 85040 - Phoenix/US
  • 4Clinical Affairs, Caris Lifesciences, Basel/CH

Abstract

Aim

Malignant phyllodes tumors constitute 0.1% of all breast tumors, which lack effective treatment options. Comprehensive molecular profiling of rare cancers holds the promise of identifying underlying pathogenetic mechanisms with potentially druggable targets.

Methods

Seventeen malignant phyllodes tumors (9 primary, 3 recurrent and 5 metastatic samples) were analyzed (Caris Life Sciences, Phoenix, AZ) using gene sequencing (NGS and Sanger), gene copy number analysis (FISH and CISH), RNA expression (RT-qPCR and whole genome microarrays) and protein expression (immunohistochemistry).

Results

Malignant phyllodes tumors showed co-expression of genes involved in angiogenesis (vascular endothelial growth factor A and its receptor KDR) in 6 of 9 cases, and additional 3 cases showed overexpression of VEGFA alone. Amplification of EGFR gene was observed in 4 of 9 tested cases, while EGFR protein overexpression (H-score ≥ 20) was observed in 10 of 11 tested cases. TP53 mutations were identified in the majority of cases tested (8/11). One metastatic tumor harbored increased cMET gene copy number. No other oncogene alterations were identified (e.g. HER2, BRAF, KRAS, PIK3CA, cKIT). DNA repair pathways were altered in 9 out of 17 cases (7/17 low ERCC1; 2/17 low BRCA1) indicating potential response to platinum agents. Low expression of TS and RRM1 (9/17 cases) indicates potential response to fluoropyrimidines and gemcitabine. Steroid receptors were uniformly negative in all cases.

Conclusions

Comprehensive tumor profiling identified diverse molecular alterations providing insight into potentially beneficial therapies in all malignant phyllodes tumors. These include novel therapies targeting angiogenesis and the EGFR pathway, as well as biomarkers of the conventional chemotherapy in this rare cancer type.

Disclosure

Z. Gatalica: Stock options Caris Life Sciences; R. Bender: Stock options Caris Life Sciences. All other authors have declared no conflicts of interest.