Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients PRINCIPAL INVESTIGATOR:

Lymph node metastases and tumor characteristics predict breast cancer prognosis but correlate imperfectly with likelihood of metastatic relapse. Discovery of genetic polymorphisms affecting metastasis may improve identification of patients requiring aggressive adjuvant therapy to prevent recurrence. We investigated associations between several variants in the BRMS1 and SIPA1 metastasis-modifying genes and lymph node metastases, tumor subtype and grade, recurrence, disease-free survival, and overall survival. This cross-sectional and prospective prognostic analysis included 859 patients who received surgery for incident breast cancer at Roswell Park Cancer Institute, participated in the DataBank and BioRepository shared resource, and had DNA, clinical, and pathology data available for analysis. Genotyping for BRMS1 (rs11537993, rs3116068, and rs1052566) and SIPA1 (rs75894763, rs746429, rs3741378, and rs2306364) polymorphisms was performed using Sequenom iPLEX Gold and Taqman real-time PCR assays. Logistic and Cox proportional hazards regressions were used to estimate odds ratios (OR) and hazard ratios (HR), respectively. BRMS1 rs1052566 heterozygous individuals were more likely to have node-positive tumors (OR = 1.58, 95 % CI 1.13–2.23), although there was no dose–response relationship, and those with at least one variant allele were less likely to have the luminal B subtype (AG ? AA: OR = 0.59, 95 % CI 0.36–0.98). BRMS1 rs3116068 was associated with increased likelihood of having the luminal B and the HER2-enriched tumor subtype (Ptrend = 0.03). Two SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple-negative tumors (Ptrend = 0.04 and 0.07, respectively). Presence of 8 or more risk alleles was associated with an increased likelihood of having a node-positive tumor (OR = 2.14, 95 % CI 1.18–3.36, Ptrend = 0.002). There were no significant associations with survival. Polymorphisms in metastasisassociated genes may be related to tumor characteristics and lymph node metastasis, but not survival. Future M. R. Roberts (&) C.-C. Hong S. Yao C. B. Ambrosone Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA e-mail: [email protected] C.-C. Hong e-mail: [email protected] S. Yao e-mail: [email protected] C. B. Ambrosone e-mail: [email protected] M. R. Roberts J. L. Freudenheim Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY 14226, USA e-mail: [email protected] S. B. Edge Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA e-mail: [email protected] W. Bshara Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA e-mail: [email protected] M. J. Higgins Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA e-mail: [email protected] 123 Breast Cancer Res Treat (2013) 139:873–885 DOI 10.1007/s10549-013-2601-3