Hormone therapy is a go-to treatment for estrogen receptor-positive breast cancer and is often very effective. However, about half of patients who get this treatment don’t see the same benefits as others. A new approach may be able to determine who will respond well and who won’t.
Researchers from Washington University School of Medicine in St. Louis developed an imaging test that measures how well estrogen receptors are functioning in a patient’s cancer cells. They found that high functioning estrogen receptors led to stable or improved outcomes with hormone therapy, while nonfunctional estrogen receptors saw cancer continue to progress, despite the hormone therapy. The results were published in the February 2 edition of Nature Communications.
Senior author Dr. Farrokh Dehdashti, along with Dr. Barry A. Siegel and Dr. Marilyn J. Siegel, says, “If breast cancer in a patient is estrogen receptor-positive, doctors will usually recommend hormone therapy even though they know it will only work for slightly more than half the patients. When hormone therapy works, it’s typically quite effective, and it has milder side effects than some other therapies, and that’s why oncologists and patients want to try it first. But we need to narrow down who is likely to benefit, and there really hasn’t been a reliable test to accomplish that.”
Around 80% of breast cancer cases are estrogen-receptor positive. That means the cancer cells carry estrogen receptors and the tumor grows due to naturally occurring estrogen in the body. Doctors use hormone therapy to attempt to block the effects estrogen has on the tumor. This can be done through a variety of drugs, including those that prevent the body from making estrogen and those that specifically block the estrogen receptor on cancer cells. Pre-menopausal women usually have a different type of hormone therapy because their bodies are still producing large amounts of estrogen.
The researchers say doctors have long believed that the women who don’t respond well to hormone therapy don’t have functioning estrogen receptors within their cancer cells, and the team at Washington University School of Medicine took this theory into mind with an imaging test.
When estrogen receptors are stimulated, cells respond by producing more progesterone receptor molecules on their surfaces. Researchers developed an imaging agent that measured the number of progesterone receptors on those cells. The compound attaches to the receptors and can be detected as part of a positron emission tomography (PET) scan. The PET signal increases with higher levels of progesterone receptors.
The study applied this method to 43 postmenopausal women with estrogen receptor-positive breast cancer, 86% of whom had metastatic disease. Nearly three-quarters had already received some kind of treatment, usually a type of hormone therapy. The women had an initial PET scan, followed by another after they’d been administered three doses of estrogen over a 24-hour period.
The PET signal in the tumor increased substantially after estrogen exposure in 28 women, meaning their estrogen receptors were working. The other 15 saw little impact. After this, researchers followed the participants for six months throughout their hormone therapy. Of the 15 who had little reaction to the estrogen, all saw their tumors progress. The ones who saw a reaction to the estrogen, meanwhile, all either improved or held stable.
Dehdashti says, “The goal of therapy is to control or improve disease, so if the therapy is likely to be ineffective, it should not be given to a patient. We observed 100% agreement between the response to estrogen challenge and the response to hormone therapy, even though the participants were on a variety of treatment regimens. This method should work for any therapy that depends on a functional estrogen receptor, and it could provide valuable information to oncologists deciding how best to treat their patients.”
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To confirm their results, the researchers are now working on getting a larger phase 2 clinical trial underway.
The American Cancer Society says hormone therapy can be used before or after surgery to lower the risk of a recurrence of cancer. It will typically be used for at least five to ten years. It also serves as a treatment for those who have seen their cancer return or spread.
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