Why Tamoxifen Works Better for Some People
Gut bacteria influence tamoxifen effectiveness, highlighting the potential for personalized breast cancer treatment.
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A new study has shown that variation in the microbiota of the human gut impacts the pharmacokinetics of tamoxifen and thus the effectiveness of the drug. The finding, published in the journal mBio of the American Society for Microbiology, suggests that in the future, doctors may use a simple test on a patient’s stool to check for certain bacteria in the gut that might help predict whether tamoxifen will work for them.
“The key takeaway from this study is that while tamoxifen is a common and important treatment for preventing breast cancer recurrence, nearly 50% of patients don’t respond well to it,” said lead study author Yasmine Alam, a Ph.D. candidate in the Department of Biological Chemistry, University of California Irvine. “Since tamoxifen is taken orally and passes through the gut, this difference in how patients respond may be linked to the gut microbiome—the trillions of bacteria in our intestines, which vary greatly from person to person. Our study aims to better understand how these gut bacteria influence the way tamoxifen is absorbed, broken down and recycled in the body, with the goal of improving treatment outcomes for breast cancer patients.”
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Subscribe for FREEWhen a person swallows a tamoxifen pill, it passes through their stomach and into their intestines, where it is absorbed into the bloodstream. Once in the blood, tamoxifen makes its way to the liver, where the drug is changed into a form that is more effective at fighting breast cancer. However, a sugar molecule can sometimes get attached to it, which signals the body to dump the cancer-fighting form of the drug back into the intestine, instead of into the bloodstream where it can then move to the parts of the body where it needs to fight the cancer. This drug can only get out of the intestine by taking the sugar off the molecule—and the researchers found that beta-glucuronidase in gut bacteria can eat the sugar off the drug so it can go on to fight breast cancer.
“Specifically, we found that certain enzymes produced by gut bacteria, called β-glucuronidase, play a role in how tamoxifen is broken down. These enzymes help recycle tamoxifen back into the bloodstream, which can make the drug more effective,” Alam said. “We discovered that a particular type of bacteria, Bacteroides fragilis, was strongly linked to the ability of these enzymes to affect tamoxifen levels in the blood in a positive way. This suggests that the gut microbiome plays an important role in how tamoxifen works in the body.”
The long-term goal of the study is to pave the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.
Reference: Alam Y, Hakopian S, Ortiz De Ora L, et al. Variation in human gut microbiota impacts tamoxifen pharmacokinetics. Fraser CM, ed. mBio. 2024:e01679-24. doi: 10.1128/mbio.01679-24
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