BPA and Breast Cancer

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Bisphenol A and Chemoresistance in Breast Cancer Cells

IFC Evaluation of Study on Bisphenol A and Chemoresistance in Breast Cancer Cells

A study published in the October 2008 edition of Environmental Health Perspectives titled, “Bisphenol A at Low Nanomolar Doses Confers Chemoresistance in Estrogen Receptor Alpha Positive and Negative Breast Cancer Cells”1 found that 24 hour pretreatment of cells with free Bisphenol A (BPA) increased the chemoresistance of two breast cancer cell lines in vitro.  This study, however, has some major limitations which reduce the applicability of its findings.

The study was performed on two isolated breast cancer cell lines, not on breast cancer in vivo.  Human cancer cells growing in culture can behave vastly different than they do in the environment that cancer cells normally experience in the body, where cells might be exposed to thousands of nutrients, hormones, and other substances, as well as BPA, that they come into contact with via the blood supply.  Currently, nothing is known about the interactions between BPA and these substances and the overall effect on cancer cells in vivo.  Since the study was performed on breast cancer cell lines rather than on laboratory animals, the study does not include absorption, metabolism, distribution, and excretion of BPA or of the chemotherapeutic drugs applied.  In this study, BPA was applied to the cell lines as free BPA, which is not how it circulates in the human body.  It has been shown that BPA is glucuronidated in the human body, thus dramatically limiting its estrogenic activity to virtually no activity.  Thus, any evaluation of the effects of free BPA in model systems has limited relevance to humans.

An additional criticism of this study is that the concentrations of the chemotherapeutic agents, which act to kill cancerous cells, were very low compared with the circulating plasma levels of these drugs, as observed in patients receiving the drugs for cancer therapy.  According to a 2006 study that administered one of these chemotherapeutic drugs (doxorubicin) at a does of 30-50 mg/square meter of body surface area, peak plasma levels were 19-34 mcg/mL2, which is 152-270 fold higher than the highest concentration used in this study.  Therefore, the chemotherapeutic drugs used in this study were not used at the strength needed for their maximum cell killing effects, making it more likely that interactions with other molecules, such as BPA, could inhibit such cell killing.

Another criticism is that the half life of BPA and some chemotherapeutic drugs like doxorubicin used in this study are greatly different.  The half-life of BPA in the blood is less than six hours, whereas, the half life of doxorubicin in the study was 86-95 hours.  Thus, even when BPA is gone from the body, there is likely ample of doxorubicin still present to exert its effects.  It is doubtful that any short term effect of BPA would have a significant long lasting effect on the activity of a doxorubicin on cell killing in vivo.  The authors of this study bypassed this relevant issue by exposing the cells to both BPA and the chemotherapeutic agents continuously over 24-96 hours, an unrealistic exposure time. 

In conclusion, this study was conducted under artificial and unrealistic conditions and the relevance of the results to chemotherapy resistance and to other health effects as well was not demonstrated.  The limitations of the doses used and the cell model system reduce the applicability of the findings.

Studies Cited:
1  LaPensee, E. W., Tuttle, T.R., Fox, S.R., and Ben-Jonathan, N., Bisphenol A at Low Nanomolar Does Confers Chemoresistance in Estrogen Receptor Alpha Positive and Negative Breast Cancer Cells.. Environmental Health Perspectives, 116(10); October 2008.

2  Fujisaka et al.  Phase 1 clinical study of pegylated liposomal doxorubicin (JNS002) in Japanese patients with solid tumors.  Japan Journal of Clinical Oncology; 36; 768-74; 2006.