Bisphenol A induces a profile of tumor aggressiveness in high-risk cells of breast cancer patients
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. Keywords: Gene expression, Epithelial, Breast cancer
Cancer Type: Breast Cancer
GPL: 570
Number of Genes with Data: 978
Number Observations: 24
Number Outputs: 1
Imbalanced Ratio: 1
Default Task: Classification