Transcription profiling by array of human breast cancers after treatment with progesterone or progesterone and bisphenol A

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. Experiment Overall Design: The study included twelve patients undergoing breast biopsy or surgery for breast cancer. Random periareolar fine needle aspirates (RPFNA) were collected from the unaffected contralateral breast of these patients. Control and hormone treated RPFNA cell cultures were analyzed using Affymetrix GeneChip(TM) arrays