Whole Genome Sequencing To Characterize Luminal-Type Breast Cancer

503 Background: To correlate clinical features of estrogen receptor positive breast cancer with somatic mutations, massively parallel sequencing (MPS) was applied to tumor and normal DNAs accrued from patients treated with neoadjuvant aromatase inhibitors (AI). Methods: MPS was applied to 77 baseline tumor biopsy samples from the preoperative letrozole trial (JACS 2009: 208, 906) and the Z1031 trial (JCO 2011: 29, 2342) followed by targeted sequencing in another 240 trial samples. Standard statistical approaches were used to compare mutation status and clinical parameters and pathway-based correlation was used to assess interactions between signaling perturbations induced by gene mutations and response to neoadjuvant AI. Results: Eighteen genes were significantly mutated above background. Aside from PIK3CA mutations, the list is dominated by loss-of-function mutations in tumor suppressor genes. Five (RUNX1, CBFP, MYH9, MLL3 and SF3B1) have been previously linked to benign and malignant hematopoietic disor...