602 Background: Aromatase (CYP19A1) is the main enzyme implicated in estrogen biosynthesis. Polymorphisms in CYP19A1 can affect both aromatase expression and activity leading to changes in the estrogen levels. These changes have been previously associated with pathogenesis of estrogen-dependent diseases, including breast cancer. The purpose of this study is to evaluate whether the genotype of CYP19A1 can have an effect on the response to endocrine therapy with the aromatase inhibitor letrozole (L). Methods: We retrospectively analyzed a series of 58 postmenopausal women with stage II-III ER/PgR[+] breast cancer treated with L as neoadjuvant therapy. Response was evaluated by radiology (mammogram or ultrasound) at four months L (OMS) and data was available in 56 cases. A total of ten single nucleotide polymorphisms (SNPs) spanning the gene, a TCT insertion/deletion and a (TTTA)n repeat were evaluated. The (TTTA)n repeat was analyzed by using GeneScan to detect polymorphism length, TCT Ins/Del by direct sequencing and SNPs by allelic discrimination using TaqMan SNP Genotyping Assays (Applied Biosystems). Logistic regression analysis was used to estimate the most accurate predictive model for response to therapy. Results: Median age of our series was 77 years (range: 68 to 90). Twenty women (36%) responded to 4 months L, while 38 (67%) did not (2 PD and 36 EE). Allelic frequencies were determined for each polymorphism and the global genotype data was evaluated in a logistic regression analysis. In a first step, the analysis with the genetic information for the 12 polymorphisms resulted in a model that predicted radiological response to L with an accuracy of 80% (85% specifity, 69% sensibility). However, a reduction to 4 informative polymorphisms generated a simpler predictive model with an accuracy of 76% (76.5% specifity, 75% sensibility). Conclusions: Polymorphism analysis of CYP19A1 could predict for response to neoadjuvant therapy with L. A validation of this predictive model in an independent series is ongoing. No significant financial relationships to disclose.