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 t...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2008-04, Vol.68 (7), p.2076-2080
Main Authors: DAIRKEE, Shanaz H, SEOK, Junhee, CHAMPION, Stacey, SAYEED, Aejaz, MINDRINOS, Michael, WENZHONG XIAO, DAVIS, Ronald W, GOODSON, William H
Format: Article
Language:English
Subjects:
Adult
Antineoplastic agents
Benzhydryl Compounds
Biological and medical sciences
Biopsy, Fine-Needle
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Epithelial Cells - pathology
Female
Gene Expression - drug effects
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Phenols - pharmacology
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-6526