Abstract PD8-05: Genomic profiling of metastatic invasive lobular carcinoma reveals unique genomics and therapeutic opportunities

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-02, Vol.78 (4_Supplement), p.PD8-05-PD8-05
• Main Authors: Sokol, ES, Basudan, A, Lee, AV, Stephens, PJ, Frampton, GM, Oesterreich, S, Hartmaier, RJ
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.SABCS17-PD8-05

Background Invasive lobular carcinoma (ILC) is a common breast cancer histological subtype comprising ˜10-15% of all cases. ILC possesses many unique features when compared to invasive ductal carcinoma (IDC). First, ILC has distinct genomic alterations expanding beyond the defining event of CDH1 loss to other genes such as TBX3, FOXA1, and AKT signaling related genes. Second, ILC responds differently to chemotherapeutics and endocrine therapies despite similar clinical staging. Third, ILC tumors spread to a distinct set of organs compared to IDC tumors, commonly forming distant metastases in the ovary, colon, omentum, and stomach. However, the genomics of metastatic ILC have yet to be fully explored. Methods Comprehensive hybrid-capture based genomic analysis of 286-395 cancer related genes was performed on 5523 histologically defined ILC (n=613) and IDC (n=4910) tumors. Of these, 29% and 21% were from distant metastatic sites for ILC and IDC, respectively. Additionally, histology based ER-status was available for a subset of tumors allowing a subgroup of ER-positive, HER2-negative IDC (ER-IDC) samples to be identified (n=655). Results We examined the genetic differences between ILC and IDC in the context of both local and metastatic disease. Overall, the genomic profiles of ILC are enriched for alterations in CDH1, TBX3, PIK3CA, and RUNX1 in agreement with previous studies. Alterations in genes involved in AKT signaling (PIK3CA, PTEN, and AKT1) are also enriched in ILC (64% v. 49%; p