New research from the Washington University School of Medicine in St. Louis has found that an imaging test measuring the function of estrogen receptors (ERs) in breast cancer cells could identify patients who are unlikely to benefit from hormone therapy.

Hormone therapy is frequently prescribed as a targeted treatment for women whose cancer cells carry receptors for estrogen, but the therapy only works for approximately half of all patients, according to the study. There has historically been no reliable way to predict which patients will benefit, although the researchers hope their findings could fulfill this need.

In a small phase 2 clinical trial, the investigators showed that the cancers of all patients with working ERs remained stable or improved on hormone therapy, although cancer progressed in all women with nonfunctional estrogen receptors. The findings, published in Nature Communications, could help physicians choose appropriate treatment options and reduce the chances that women receive a therapy unlikely to help, according to the authors.

“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,” said senior author Farrokh Dehdashti, MD, a professor of radiology at the Mallinckrodt Institute of Radiology, in a press release. “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.”

Approximately 4 out of 5 breast cancers in the United States are labeled ER-positive, which means the cancer cells carry ERs and the tumor grows in response to the naturally occurring hormone estrogen. Hormone therapy is designed to stop the effects of estrogen on the tumor, according to the researchers.

Physicians typically choose a hormone therapy regimen based on the patient and the specifics of their disease. Aromatase inhibitors prevent the body from making estrogen and are typically the first treatment chosen for hormone therapy, according to the press release, whereas fulvestrant blocks the ER on cancer cells. These drugs are usually given to postmenopausal women, whereas pre-menopausal women are given different therapies because their ovaries are still producing large amounts of estrogen.

To measure the functionality of ERs, the investigators utilized a link between the ER and a progesterone receptor (PR). When ERs are stimulated, the cells respond by increasing the number of PR molecules on their surfaces, according to the study authors.

John Katzenellenbogen, PhD, designed an imaging agent to probe the number of PRs on the surface of cancer cells, in collaboration with Michael Welch, PhD. The compound, 21-[18F] fluorofuranylnorprogesterone (FFNP), attaches to PRs and can be detected with a positron emission tomography (PET) scan. When more PRs are present, the PET signal is higher.

The investigators recruited 43 postmenopausal women with ER-positive breast cancer. Most (86%) had metastatic disease, whereas 14% had locally advanced or locally recurrent disease. The majority (72%) had already received some form of treatment before the start of the study, and their prior treatment was most often a hormone therapy-based regimen. The participants underwent a PET scan using FFNP, followed by 3 doses of estrogen over a 24-hour period and a second PET scan a day after the estrogen treatment.

For 28 women, the PET signal in the tumor increased considerably after exposure to estrogen, indicating that their ERs were working and had responded to the hormone by triggering an increase in PR numbers. Fifteen women showed little to no change in PR numbers after estrogen treatment.

Then, the investigators followed the participants for 6 months or longer as they underwent hormone therapy as recommended by their individual oncologists. The disease of all 15 women whose tumors had not responded to estrogen worsened within 6 months, and of the women whose tumors had responded 13 remained stable and 15 improved.

“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,” said Dehdashti in a press release. “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.”

REFERENCE
Imaging identifies breast cancer patients unlikely to benefit from hormone therapy [news release]. Washington University School of Medicine; February 2, 2021. https://medicine.wustl.edu/news/imaging-identifies-breast-cancer-patients-unlikely-to-benefit-from-hormone-therapy/. Accessed February 3, 2021.