Researchers at Washington University School of Medicine in St. Louis have shown they can distinguish patients with breast cancer likely or unlikely to benefit from hormone therapy using an imaging test that measures the function of the estrogen receptors in their cancer cells, according to a press release from the university.
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.
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, while the disease and progressed in all women with nonfunctional estrogen receptors.
The findings, published in Nature Communications, could help doctors choose among treatment options and reduce the chances that women would receive a therapy unlikely to help.
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.
Doctors have long suspected that the difference between women who respond to hormone therapy and those who do not 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.
The researchers 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.
The researchers recruited 43 postmenopausal women with estrogen receptor-positive breast cancer. Most (86 percent) had metastatic disease, while 14 percent had locally advanced or locally recurrent disease. The majority (72 percent) 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 researchers are now in the process of setting up a larger phase 2 clinical trial with collaborators at other institutions to verify their results.
