The death rate for breast cancer in the United States has been steadily decreasing from 1989 through 2021, according to the American Cancer Society. One of the reasons is personalized treatment. A key to a personalized treatment plan is to determine whether the breast cancer is estrogen receptor-positive (ER+). Also known as estrogen-sensitive or estrogen- responsive breast cancer, this type of breast cancer has tumor cells that contain hormone receptors that allow them to grow using estrogen. Somewhere between 67% and 80% of breast cancers in women are ER+, according to the National Cancer Institute. Currently, the test used most often to determine whether a patient has cancer, including metastases and recurrences, is biopsy and immunohistochemistry (IHC).
While the results from core needle biopsies and IHC are reliable, both methods have some limitations. First, a single-location biopsy may miss ER status differences within one tumor or across multiple tumors, since different areas within a tumor may present different tumor characteristics. Second, some metastatic lesions are difficult to access, such as those in the brain. The common practice is to target the lesion which is easiest to access and has a low risk of complications rather than the lesion of most clinical significance. A third limitation of biopsy/IHC is the inability to retrieve an adequate specimen because of bleeding, bone decalcification, or some other technical reason, says Regina Munter-Young, lead author of a study published in May 2024 in PLOS ONE by GE HealthCare scientists.
Munter-Young, GE HealthCare’s head of global market access, and colleagues researched whether adding F-18 fluoroestradiol (FES)-PET/CT imaging to a woman’s breast cancer care could increase true-positive and true-negative ER test results and reduce the need for biopsies. Their conclusion was that doing so could not only increase the diagnostic accuracy of a patient’s ER status but, at the same time, save the US health care system up to $142 million over a five-year period.
The FDA approved the radiopharmaceutical F-18 FES-PET/CT for detecting ER+ lesions in patients with recurrent or metastatic breast cancer in May 2020 as an adjunct to biopsy. F-18 FES-PET was developed by the French biomarker firm Zionexa as Cerianna. (GE HealthCare acquired Zionexa in May 2021.) In June 2023, SNMMI published a procedure standard/ practice guideline for imaging breast cancer patients with F-18 FES PET/CT. In conducting their research, the scientists used diagnostic guidelines outlined in the latest version of the National Comprehensive Cancer Network breast cancer guidelines and SNMMI’s Appropriate Use Criteria.
Understanding the positive or negative status of the ER helps to determine if and how well hormone therapy might work. If a patient’s disease is ER+, then they might be a candidate for hormone therapy. If their disease is ER-negative (ER-), then they probably are not a candidate for hormone therapy. “Considering that three of every four patients with breast cancer have tumors that are ER+, the confirmation of active estrogen receptors can help guide an oncologist in their decision making to continue with hormonal therapy instead of moving to chemotherapy,” Munter-Young says.
Adding Up
The GE researchers designed their study to investigate whether F-18 FES PET/CT would contribute to diagnostic accuracy. “But a positive conclusion was not predetermined,” Munter-Young says. “The study team believed that F-18 FES PET/CT may be more accurate in specific use cases based on the difference between the positive predictive value and negative predictive value of F-18 FES PET/CT compared to biopsy/IHC. In addition, determining the functionality of the estrogen receptor and understanding the extent to which they are avid for FES may guide a more accurate selection of therapy.”
Munter-Young explains how adding F-18 FES PET/CT works: Estradiol is a hormone that ER+ cells require to grow. Hormone therapy prevents the ER+ cancer cells from getting the estradiol they need to grow. FES is a radioactive form of estradiol that, after administration, binds to functional ERs. The result is a whole-body map showing where functioning ERs are located. Cancer lesions that do not bind FES are less likely to respond to hormone therapy. “Other imaging such as CT may show the physical location of lesions but doesn’t tell the estrogen receptor status of that tissue,” Munter-Young says.
The budget impact study was based on data from studies of women with breast cancer that were published between January 1980 and May 2020. The data populated the model, which was used to evaluate the budget impact of two scenarios: A) where ER+ status was determined through biopsy/IHC alone and B) where F-18 FES PET/CT was used as an adjunct to biopsy/IHC. The analysis also investigated the costs in three specific patient sub-groups: 1) those with metastatic breast cancer whose biopsies failed or were inconclusive, 2) patients with metastatic breast cancer who were not able to have a biopsy, and 3) all those with recurrent breast cancer.
Then, they compared the cost of each scenario. Their financial calculations included the cost of the molecular imaging tracer and any other diagnostic imaging scans, biopsies, treatments, managing treatment-related adverse events, and other related care, such as end-of-life care.
Their results showed that when F-18 FES PET/CT was added to biopsy/IHC (as in Scenario B) the proportion of true-positive and true-negative test results increased from 0.2% to 8% compared with biopsy/IHC alone (Scenario A) and the need for additional biopsies was nearly eliminated. Rebiopsies were reduced by 94% to 100%, they found. “Beyond that, [we] found that F-18 FES PET/CT may provide higher diagnostic accuracy of ER+ disease for clinical dilemmas such as an inability to determine the extent of (suspected) metastatic disease with the standard workup, unclear ER status of the tumor, and an inability to determine which primary tumor caused metastases,” they wrote in their report.
While the study’s results are promising, Munter-Young says the impact of the pharmaco-economic study on health care practice remains to be determined. Munter-Young says whether F-18 FES PET/ CT would be covered by insurance is “currently evolving.” Some health plans have not yet reviewed the technology to determine if it is considered “reasonable and necessary,” despite the National Comprehensive Cancer Network’s inclusion in its guidelines, she says.
F-18 FES PET/CT scans are read by imagers who have training in radiopharmaceuticals. “They are often the same physicians reading MRI, CT, and FDG PET/CT,” Munter-Young says. “Training specific to each radiopharmaceutical is available either through the manufacturer or professional societies such as SNMMI or the ACR.”
— Beth W. Orenstein of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.