ICE/ENDO 2014: 16th International Congress of Endocrinology and The Endocrine Society's 96th Annual Meeting:
Bisphenol A (BPA): An Endocrine-Disrupting Chemical and Inflammatory Breast Cancer
Gayathri Devi, PhD, Associate Professor, Department of Surgery, at Duke University Medical Center in Durham, NC, stated, “This is the first study to show BPA’s [Bisphenol A] effects in altering the effectiveness of a targeted drug treatment [Lapatinib] approved for use in breast cancer patients, including those with inflammatory breast cancer.” Dr. Devi presented the study results, which was a collaboration between Duke University, the Environmental Protection Agency (EPA), and the Biomanufacturing Research Institute and Technology Enterprise (BRITE) at North Carolina Central University.
The goal of the study was to examine the impact of BPA on the efficacy of cancer treatment; mechanisms of resistance in inflammatory breast cancer (IBC). IBC is not actually an inflammatory process, but a subset of a locally advanced breast cancer. IBC is rare, making up only 1% to 5% of all breast cancer cases in the United States. However, the number of IBC cases seems to be rising as more physicians are becoming familiar with its diagnosis.
Dr. Devi explained his lab chose IBC as their study model because it grows rapidly, is highly metastatic, and develops a high level of resistance to treatment. Only about 34% of people with IBC survive 5 years. There are limited treatment options and these cancers are not estrogen receptor-positive, so drugs like tamoxifen are not effective.
Lapatinib, a drug that inhibits the protein epidermal growth factor receptor (EGFR) and is clinically used to treat IBC and other cancers, was the treatment choice. Lapatinib blocks growth signaling that in turn, causes a stress response in the cancer cell and eventually leads to cell death. During Dr. Devi’s presentation, he demonstrated that during a resistant paradigm, while the tumor is still being treated, the growth factor signaling continues to decline—but the stress response does not occur. The cancer cells survive leading to a poor outcome.
“We hypothesized that instead of an acquired resistance, where the patient is treated with lapatinib for two to six months before resistance develops, there are chemicals abundantly present in the environment that can target the same kind of signaling axes. And so we hypothesized that if patients are being exposed to these chemicals, signaling in the body can change and cause a decrease in the stress response that is seen in acquired resistance, leading to cell survival,” Dr. Devi explained.
Other studies have revealed Bisphenol A (BPA), a hormone-disrupting chemical found in consumer and medical products (eg, intravenous tubing) can increase the risk for cancer. Dr. Devi and colleagues collected cancer cells isolated from patients with IBC tumors and subjected the cells to BPA. The BPA doses and exposure periods (ranges of exposure time and frequencies) were analyzed.
The study found BPA actually increased the activation of EGFR, which had not been shown before. Dr. Devi stated, “And even more interestingly, because this is the actual target of lapatinib, we see that it’s almost completely obliterated when you just treat it [tumor] with the drug [lapatinib] alone, but when you add BPA, we start to reverse the direct action of lapatinib. This is a different paradigm that what’s been seen for the most part in the literature. BPA has been shown to increase the proliferation of numerous cancer cells; but this is one of the first studies looking at how it [BPA] can impact treatment outcomes."