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Two compounds that mimic estrogen may reverse the effects of certain breast cancer treatment, according to a new study. These compounds are called xenoestrogens that can reduce the efficacy of anti-estrogen breast cancer treatments.
Certain types of breast cancer rely on specific hormones to grow and flourish. One type is called estrogen-receptor-positive breast cancer. Breast cancer cells of this type receive and use estrogen that can be stopped by hormone therapy. Hormone therapy includes medications that either block or lower the estrogen levels in the system in order to slow down the growth of breast cancer cells.
- Tamoxifen is a drug that blocks estrogen receptors on breast cancer cells. It is can be used after surgery to reduce the risk of the breast cancer coming back and to lower the chance of developing new cancer on the other breast.
- Toremifene also blocks estrogen receptors but is only approved to treat metastatic breast cancer.
- Fulvestrant is a medication that blocks and damages estrogen receptors. It is used to treat metastatic breast cancer and may work with other drugs, such as tamoxifen and an aromatase inhibitor.
- Aromatase inhibitors are drugs that stop the production of estrogen by blocking the enzyme, aromatase.
"Breast cancer patients taking palbociclib/letrozole should consider limiting their exposure to foods that contain xenoestrogens," said Dr. Gary Siuzdak, the senior director of The Scripps Center for Metabolomics at The Scripps Research Institute.
Palbociclib is a drug for the treatment of ER+ breast cancer that has been prescribed over 90,000 times in December 2017. Letrozole is an aromatase inhibitor used to treat local and metastatic breast cancer. These two are used as a combination therapy since its approval in 2015 by the US Food and Drug Administration for postmenopausal women with ER+ breast cancer. The mechanism of treatment works as letrozole blocks estrogen production while palbociclib interrupts via a different signal in breast cancer cells that disrupt cell division.
Dr. Siuzdak and colleagues analyzed the effects of both medications on breast cancer cells through the use of advanced metabolomics technology. The technology allowed them to profile cell metabolomes with and without the drug to get useful information. They found that if the drugs work separately, their impact will be minimal against the disease. But together, the combined effects can impact breast cancer.
"The combination had a much more pronounced effect on cell-growth-related metabolites, which is consistent with the clinical trial results," said Dr. Benedikt Warth, from the University of Vienna and the lead author of the study.
But the concern of the cancer researchers is the growing amount of xenoestrogens in many products which may weaken ER+ breast cancer treatments and promote breast cancer growth in people. Scientists at TSRI examined breast cancer cells treated with the combination therapy and analyzed the effects of exposure to two xenoestrogens – genistein and zearalenone.
1. Genistein is a compound produced by specific plants, such as soybeans, and is often in highly concentrated levels in phytoestrogen-rich food supplements. Genistein has antioxidant and anthelmintic properties or can expel parasitic worms. Normally, the compound acts as an angiogenesis inhibitor that inhibits the growth of blood vessels, which limits the multiplication of cancer cells. However, the compound has also been found to have a high affinity towards beta-estrogen-receptors than alpha-estrogen-receptors. The compound increases the multiplication rate of ER+ breast cancer cells.
2. Zearalenone is a mycotoxin or fungi poison that replicates estrogen. It is produced by the fungi Fusarium graminearum that contaminates crops like barley, maize, and wheat. In pigs and other livestock, the mycotoxin was suggested to be associated with birth defects and abnormal sexual development, such as enlarged uterus and swelling of the vulva and the vagina.
The researchers discovered that xenoestrogens, even in low doses, reversed the therapeutic effects of the combination therapy. Breast cancer cells also multiply at the same rate when the drug was absent. The addition of the xenoestrogens in diet can affect the outcome of estrogen hormone therapy for breast cancer.
"We generally know very little about the interactions of bioactive compounds we are exposed to through our food or the environment with drug treatments. So, in this field there are probably a lot of clinically relevant discoveries yet to be made," said Dr. Warth.
Xenoestrogens are found in many products women use every day, such as in skincare products like sunscreens, in industrial products like foams and plastics, in food preparation like food preservatives, and in construction supplies like paints and wood preservatives.