Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from 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 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.
Dairkee
Shanaz H
SH
California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA. dairkes@cpmcri.org
Seok
Junhee
J
Champion
Stacey
S
Sayeed
Aejaz
A
Mindrinos
Michael
M
Xiao
Wenzhong
W
Davis
Ronald W
RW
Goodson
William H
WH
D000328:Adult; D001559:Benzhydryl Compounds; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds