Imaging identifies breast cancer patients unlikely to benefit from
hormone therapy
Findings could help improve treatment decisions

Date:
February 2, 2021
Source:
Washington University School of Medicine
Summary:
Hormone therapy can be very effective for so-called estrogen
receptor- positive breast cancer. But it only works for a little
more than half of women who receive the treatment. In a small
study, researchers found that women whose tumors did not respond
to a one-day estrogen challenge did not benefit from hormone
therapy. The findings could help doctors choose treatments most
likely to help their patients.



FULL STORY ========================================================================== Hormone therapy commonly is given as a targeted treatment for women
whose cancer cells carry receptors for estrogen. But the therapy only
works for about half of all patients. Until now, there hasn't been a
good way to reliably predict who will benefit and who will not.


========================================================================== Researchers at Washington University School of Medicine in St. Louis have
shown they can distinguish patients likely or unlikely to benefit from
hormone therapy using an imaging test that measures the function of the estrogen receptors in their cancer cells. In a small phase 2 clinical
trial, the researchers showed that the cancers of all patients with
working estrogen receptors remained stable or improved on hormone therapy,
and progressed in all women with nonfunctional estrogen receptors. The findings, published Feb. 2 in Nature Communications, could help doctors
choose among treatment options and reduce the chances that women would
receive a therapy unlikely to help.

"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, the Drs. Barry A. and Marilyn J. Siegel
Professor of Radiology at Mallinckrodt Institute of Radiology (MIR). "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 four out of five breast cancers -- some 250,000 per year in
the United States -- are labeled "estrogen receptor-positive," meaning
that the cancer cells carry estrogen receptors 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.

A variety of drugs can be prescribed as hormone therapy, and doctors
choose a treatment regimen depending on the patient and the specifics
of that person's disease. Aromatase inhibitors prevent the body from
making estrogen and are usually the first treatment chosen for hormone
therapy. Fulvestrant blocks the estrogen receptor on cancer cells. These
drugs usually are given to postmenopausal women. Pre-menopausal women
often are given different hormone therapies because their ovaries still
are producing large amounts of estrogen.

Doctors have long suspected that the difference between women who respond
to hormone therapy and those who don't comes down to whether the estrogen receptors on their cancer cells are working properly. If the receptors are present but nonfunctional, targeting them is unlikely to have much effect.



========================================================================== Dehdashti and colleagues, including co-authors Barry A. Siegel, MD, a
professor of radiology, and Cynthia Ma, MD, PhD, a professor of medicine,
set about measuring the functionality of estrogen receptors by taking
advantage of a link between the estrogen receptor and a receptor for
another hormone: progesterone.

When estrogen receptors are stimulated, cells respond by increasing the
number of progesterone receptor molecules on their surfaces.

Co-author John Katzenellenbogen, PhD, a chemist at the University of
Illinois, designed an imaging agent to probe the number of progesterone receptors on the surface of cancer cells, in collaboration with the
late Michael Welch, PhD, then a professor of radiology at Washington University. The compound, 21-[18F] fluorofuranylnorprogesterone (FFNP), attaches to progesterone receptors and can be detected with a positron
emission tomogrophy (PET) scan. When more progesterone receptors are
present, the PET signal is higher.

The researchers recruited 43 postmenopausal women with estrogen receptor- positive breast cancer. Most (86%) had metastatic disease, while 14% had locally advanced or locally recurrent disease. The majority (72%) already
had received some form of treatment before the start of the study. Their
prior treatment was most often a hormone therapy-based regimen.

The women underwent a PET scan using FFNP, followed by three doses of
estrogen over a 24-hour period, and then 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 estrogen receptors were
working and had responded to the hormone by triggering an increase in progesterone receptor numbers. Fifteen women showed little to no change
in progesterone receptor numbers after estrogen treatment.

Then, the researchers followed the participants for six 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 six months. 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, who is also senior vice chair and division director of
nuclear medicine at MIR.

"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." The researchers are now in the process of setting up
a larger phase 2 clinical trial with collaborators at other institutions
to verify their results.


========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Farrokh Dehdashti, Ningying Wu, Cynthia X. Ma, Michael J. Naughton,
John
A. Katzenellenbogen, Barry A. Siegel. Association of PET-based
estradiol- challenge test for breast cancer progesterone receptors
with response to endocrine therapy. Nature Communications, 2021;
12 (1) DOI: 10.1038/ s41467-020-20814-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/02/210202101043.htm

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