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Bisphenol A Induces a Profile of Tumor Aggressiveness in High-Risk Cells from Breast Cancer Patients

¹ California Pacific Medical Center Research Institute, San Francisco, California and ² Stanford Genome Technology Center, Stanford University School of Medicine, Palo Alto, California

Requests for reprints: Shanaz H. Dairkee and William H. Goodson, California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA 94107. Phone: 415-600-1653; Fax: 415-600-1725; E-mail: dairkes{at}cpmcri.org (S.H. Dairkee) and Phone: 415-923-3925; Fax: 415-776-1977; E-mail: goodsow{at}cpmcri.org (W.H. Goodson).

Key Words: RPFNA • Xenoestrogen • Gene expression • Histologic grade • Prognosis

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 used nonmalignant random periareolar fine-needle aspirates in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of patients with breast cancer included gene expression patterns which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell numbers. 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 show 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. [Cancer Res 2008;68(7):2076–80]