Abstract P2-08-03: Patterns of somatic mutations in metaplastic carcinoma of the breast

Abstract

Abstract Introduction Metaplastic carcinoma of the breast (MCB) is a heterogeneous group of malignant tumors comprising less than 1% of all breast carcinomas encompassing tumors with purely epithelial, as well as epithelial and mesenchymal components, which may be entirely metaplastic or admixed with carcinoma. There is no agreed upon optimal treatment regime for these tumors, which overall have a worse prognosis than similar stage invasive ductal carcinoma (IDC). Research into MCB has been limited by the rarity of this tumor; however as the majority of these tumors do not express ER, PR or Her2 (triple negative) and response to traditional chemotherapy is limited, there is a need for further research to identify predictive biomarkers and new targets for treatment. We report our findings of multigene mutation profiling in a series of 21 MCB. Methods DNA was extracted from tumors of twenty one patients with MCB, genotyped using the Oncocarta v1.0 kit a sensitive, high throughput mass spectrometry based assay which detects a panel of 238 specific mutations in 19 oncogenes including KRAS, BRAF, PIK3CA, MET, AKT1 & ERBB2 and processed on the Sequenom compact MassARRAY platform. In the case with heterologous differentiation, separate cores were taken from the spindle cell, osteo- and chrondrosarcomatous areas. Results Histological review revealed three pure spindle cell cases with the remainder showing mixed patterns of spindle, squamous and IDC, no special type. A single case showed heterologous osteosarcomatous and chondrosarcomatous differentiation. Ten mutations were detected in these 21 MCB. PIK3CA gene mutations (six H1047L and one E545K mutation) were seen in seven patients; and KRAS gene mutations (two G12V and one G12A) were observed in three patients. No mutations were detected in the case with heterologous elements in the separate areas of spindle, osteo- and chondrosarcomatous differentiation. Conclusions PIK3CA mutations were seen in 33% and KRAS mutations were seen in 14% of MCB cases in this series. Given the general lack of effective chemotherapies in MCB, these findings suggest that the PI3K pathway may be a promising therapeutic target worthy of further investigation. We plan to also undertake detailed mutational analyses using next generation sequencing to identify further potential therapeutic targets in these rare and difficult to treat malignancies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-08-03.