Environmental exposure to the industrial chemical bisphenol A (BPA) lowers the effectiveness of a targeted anti-cancer drug for inflammatory breast cancer, according to a new study that was performed in human cancer cells. The results, which were presented Sunday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago, also show that BPA causes breast cancer cells to grow faster.
“Routine exposures to common environmental chemicals like BPA appear to contribute to breast cancer cell progression and to diminish drug treatment efficacy, particularly in inflammatory breast cancer,” said principal investigator Gayathri Devi, PhD, associate professor, Department of Surgery, Duke University Medical Center, Durham, N.C.
Inflammatory breast cancer is a rare, aggressive form of breast cancer with one of the worst survival outcomes due to high rate of treatment failure.
“Not everyone with inflammatory breast cancer responds to treatment, and environmental factors are one of many factors thought to explain why,” Devi said.
Other studies have pointed to increased cancer risk with exposure to BPA, a hormone-disrupting chemical found in many consumer products, including hard plastics. However, Dr. Devi said, “This to the best of our knowledge is the first study to show BPA’s effects in altering effectiveness of a targeted drug treatment approved for use in breast cancer patients including those with inflammatory breast cancer.”
This study is a collaboration between Duke University, the Environmental Protection Agency, NC (EPA) and the Biomanufacturing Research Institute and Technology Enterprise (BRITE) at North Carolina Central University. The EPA’s library of chemicals called Toxicity Forecaster or ToxCast, a panel of approximately 300 environmental compounds was used in a newly developed automated screening technology for assessing cancer cell behavior parameters. These "high-content, high throughput screening” assays expose living cells to various doses of chemicals and allow for studying of changes in cell growth and survival.
Devi and colleagues subjected cancer cells isolated from the tumors of patients with inflammatory breast cancer to BPA and other common environmental contaminants in the ToxCast library. They tested a wide range of BPA doses and periods of exposure time including the range observed in human blood samples and from environmental exposures in past, published studies. The researchers then analyzed the cellular changes in culture and compared them with cancerous cells not exposed to BPA.
Although BPA is known to mimic estrogen, it also affected inflammatory breast cancer, which are frequently estrogen receptor-negative, meaning they do not respond to estrogen. BPA exposure caused breast cancer cells to grow faster than untreated cancer cells regardless of whether the cancer was estrogen receptor-positive or -negative, the investigators found.
In addition, this study reported that BPA lowered the effectiveness of an approved cancer-fighting drug, lapatinib, used in breast cancer therapy. Other FDA approved anti-cancer drugs are currently being tested by this team. Devi said the results may have immediate implications in cancer treatment. “Cancer patients must understand there’s a component in their daily lives that could influence their treatment outcome. These studies provide the foundation for additional research to develop tools that can be used to identify patients who may be at greater risk of developing treatment resistance. Further, the findings could also lead to biomarkers that identify patients who have heavy exposure to chemicals that could diminish the effectiveness of their cancer therapy.” Dr. Devi stated. Scott Sauer, a research fellow in the Devi Laboratory in Duke’s Department of Surgery, will present the research.
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