News | PET Imaging | February 03, 2021

Imaging Identifies Breast Cancer Patients Unlikely to Benefit from Hormone Therapy

The study's findings could help improve treatment decisions

Bright spots indicate that cancer cells have responded to a one-day challenge with estrogen in this positron emission tomography (PET) scan of a woman with breast cancer. In a small study, researchers at Washington University School of Medicine in St. Louis found that only women whose tumors responded to estrogen challenge benefited from hormone therapy. The findings could help doctors choose the treatments most likely to help their patients. Image courtesy of Farrokh Dehdashti

Bright spots indicate that cancer cells have responded to a one-day challenge with estrogen in this positron emission tomography (PET) scan of a woman with breast cancer. In a small study, researchers at Washington University School of Medicine in St. Louis found that only women whose tumors responded to estrogen challenge benefited from hormone therapy. The findings could help doctors choose the treatments most likely to help their patients. Image courtesy of Farrokh Dehdashti

February 3, 2021 — 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, M.D., 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, M.D., a professor of radiology, and Cynthia Ma, M.D., Ph.D., 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, Ph.D., 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, Ph.D., 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.

For more information: www.medicine.wustl.edu

Related Content

IBA (Ion Beam Applications S.A., EURONEXT), a world leader in particle accelerator technology, and SCK CEN (Belgian Nuclear Research Center) announced a strategic R&D partnership to enable the production of Actinimum-225 (225Ac), a novel radioisotope which has significant potential in the treatment of cancer.
News | Radiation Oncology | September 17, 2021
September 17, 2021 — IBA (Ion Beam Applications S.A., EURONEXT), a world leader in particle accelerator technology, a
Evaluation of therapeutic efficacy of drug candidates in preclinical oncology with positron emission tomography (PET)

Getty Images

Feature | PET Imaging | September 14, 2021 | By Todd Sasser, Ph.D.
With a wealth of landmark studies in Breast, Cervical, Melanoma, Prostate, Colorectal, Oesophagus, Endocrine and Lung cancer, the ESMO Congress 2021 is a clear demonstration that oncology research has once again gathered momentum after being temporarily stopped in its tracks by the outbreak of the virus

Getty Images

News | Radiation Oncology | September 13, 2021
September 13, 2021 — At the opening press conference of the ...
Plan to attend RSNA21 at McCormick Place Chicago, Nov. 28 – Dec. 2, 2021

Getty Images

News | RSNA | September 13, 2021
September 13, 2021 — The Radiological Society of North America (RSNA) today announced highlights of the Technical Exh
Laws designed to help women with increased risk for missed breast cancer diagnoses may help catch the disease earlier, according to Penn State College of Medicine researchers.

Getty Images | AleksandarNakic

News | Breast Imaging | September 09, 2021
September 9, 2021 — Laws designed to help women with increased risk for...
Comment letters on the 2022 physician fee schedule and Radiation Oncology Model urge CMS to scale back extreme cuts that jeopardize access to life-saving cancer treatments

Getty Images

News | ASTRO | September 09, 2021
September 9, 2021 — The American Society for Radiation Oncology (AS...

Image of a STING protein, courtesy of UCLA Jonsson Comprehensive Cancer Center

News | PET Imaging | September 08, 2021
September 8, 2021 — A new study from scientists at the UCLA Jonsso...
An artificial intelligence (AI) program can spot signs of lung cancer on computed tomography (CT) scans a year before they can be diagnosed with existing methods, according to research presented at the European Respiratory Society International Congress.

Diagram showing details of the lung screening experiment. Image courtesy of the European Respiratory Society/Benoit Audelan

News | Artificial Intelligence | September 08, 2021
September 8, 2021 — An artificial intell...