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Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations, which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we employed non-malignant random periareolar fine needle aspirates (RPFNA) in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of breast cancer patients included gene expression patterns, which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell number. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (p<0.001), and large tumor size (p=0.002), resulting in decreased recurrence-free patient survival (p<0.001). Our assays demonstrate a biological “fingerprint” of probable prior exposure to endocrine disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA