Imaging Agent May Provide Early Info About Benefits of Hormone Therapies for Breast Cancer

A new imaging agent that successfully measures changes in progesterone receptor (PR) levels may be used to determine if a breast cancer patient will respond to hormone therapies targeting the estrogen receptor (ER), a study suggests.

The study, “Sensitivity and Isoform Specificity of ¹⁸F-Fluorofuranylnorprogesterone for Measuring Progesterone Receptor Protein Response to Estradiol Challenge in Breast Cancer,” was published in the Journal of Nuclear Medicine.

Breast cancer patients whose disease is positive for the ER — the most common form of the disease — normally are treated with some form of hormone therapy targeting the ER.

But first, doctors normally administer a short course of estrogen treatment —  called a estradiol challenge — to determine if a patient is likely to benefit from these approaches.  This is done by monitoring changes in PR levels during treatment, which increase in the presence of estrogen.

Several imaging agents have been developed to monitor and examine changes in PR levels, and researchers at the University of Wisconsin School of Medicine and Public Health now studied if the 18F-fluorofuranylnorprogesterone (18F-FFNP) imaging agent could be used for that purpose.

The 18F-FFNP has been used for identifying PR-positive breast cancer in one study, where it also was found safe and highly specific to PR proteins.

“Typically, anatomic size and proliferation biomarkers are analyzed to determine endocrine sensitivity,” Amy M. Fowler, MD, PhD, said in a press release. Fowler is an assistant professor in the department of radiology, at the University of Wisconsin-Madison. “However, non-invasive detection of changes in PR expression with 18F-FFNP during an estradiol challenge may be an earlier indicator of the effectiveness of a specific hormone therapy,” she said.

The imaging agent, made for positron emission tomography (PET) scans, was tested in breast cancer cells that produced both the ER and PR. After being challenged with estradiol (a type of estrogen) these cells produced more PR, which was detected effectively with 18F-FFNP.

The findings were confirmed in mice implanted with the same breast cancer cells, where 18F-FFNP uptake also correlated with an increase in PR levels after the estradiol challenge.

Importantly, while the progesterone receptor has two main variants — called PR-A and PR-B — the team showed that 18F-FFNP identified changes in both forms of the receptor. “This is an important finding given the variability of PR [variant] expression observed in breast cancer patients,” said Fowler.

Together, the findings confirm that 18F-FFNP can accurately and non-invasively measure changes in PR levels, which could be used to determine sensitivity to hormone therapies targeting the ER.

“18F-FFNP is capable of measuring estrogen-induced shifts in total PR expression in human breast cancer cells and [animal models] with equivalent [variant] binding,” researchers concluded.

“Validation of PR imaging as a biomarker of endocrine sensitivity in patients before and after estradiol challenge could provide new opportunities in the field of molecular imaging and nuclear medicine for breast cancer imaging,” Fowler said. “Improved methods for testing endocrine sensitivity in patients could better inform decisions for optimal individualized ER-positive breast cancer therapy, potentially reducing morbidity and mortality.”

A Phase 2 clinical trial (NCT02455453), currently recruiting participants, is already testing if this approach could be used for ER-positive, HER2-negative breast cancer patients scheduled to receive standard-of-care hormone therapy.

Eligible participants have newly-diagnosed locally advanced or metastatic disease, or failed prior breast cancer treatments, and will receive 18F-FFNP on two separate occasions: one before a one-day estradiol challenge, and another immediately after.