Abstract 4798: Genomic alterations in ERBB2 define a subset of pleomorphic invasive lobular breast cancer

Abstract Background. Pleomorphic invasive lobular carcinoma represents a unique histologic subset of breast cancer with poorer outcomes as compared with classic invasive lobular carcinoma of the breast. With the recent finding of ERBB2 alterations in recurrent invasive lobular carcinoma, the goal of this study is to define the relationship of ERBB2 alterations in the distinct subset of pleomorphic invasive lobular carcinomas. Methods. Using the provisional invasive breast cancer data set of 962 cases in The Cancer Genome Atlas (TCGA), all breast cancers with CDH1 alterations were identified and pathologic review was performed. Independent identification of ERBB2 genomic alterations was done. The frequency and nature of genomic alterations in ERBB2, PTEN, PIK3CA, and TP53 were determined. FFPE specimens from an additional 18 cases from our own institution have been evaluated using the combination of the RainDance ThunderBolts™ Cancer Panel for validation. Results. Of 116 TCGA breast cancers with CDH1 alterations, 86 were invasive lobular breast cancer. Within this subset, 21 pleomorphic lobular breast cancers were identified based on morphologic review. Nine ERBB2 mutations (42.9%) and three amplifications (14.3%) were found in pleomorphic invasive lobular carcinoma, but none in classic invasive lobular carcinoma (p value 1.92e-9). There were no significance differences in the frequency of TP53, PTEN or PIK3CA alterations in pleomorphic invasive lobular carcinoma as compared to classic invasive lobular carcinoma. Data from the additional 18 validation cases will be presented. Conclusions. Genomic alterations in ERBB2 strongly associate with the finding of pleomorphic invasive lobular but not classic invasive lobular histology. The presence of ERBB2 alterations has therapeutic implications specific to this rare breast cancer subset that could impact outcomes. Comprehensive genomic profiling identifies ERBB2 mutations that are not detected with standard clinical immunohistochemistry or FISH. Citation Format: Kim M. Hirshfield, Renee Sanders, Heather K. Feld, Nicola Barnard, Li Liang, Hua Zhong, Gyan Bhanot, Amrik S. Sahota, Andrew Brooks, Lorna Rodriguez-Rodriguez, Shridar Ganesan. Genomic alterations in ERBB2 define a subset of pleomorphic invasive lobular breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4798. doi:10.1158/1538-7445.AM2015-4798