Original studyCan Fluorine-18 Fluoroestradiol Positron Emission Tomography–Computed Tomography Demonstrate the Heterogeneity of Breast Cancer In Vivo?
Introduction
Breast cancer is the most common nondermatologic cancer and the second leading cause of cancer death in women.1 The status of the estrogen receptors (ER) is of prime importance in breast cancer to choose the appropriate therapeutic approach and to determine the prognosis of the illness.2, 3, 4 Approximately 75% of the tumors express the ER at diagnosis.5 However, not all the patients respond to the endocrine therapy, and most initial responders later become refractory: the objective response rate to second-line endocrine therapy is less than 20%.6 One factor hypothesized to underlie unpredictable response and acquired resistance to endocrine therapy is heterogeneity of ER expression. Because the ER status may be discordant within the same patient, a single biopsy may not be representative of the ER characteristics of the tumor burden as a whole.7 In addition, ER expression may also change over time in the same patient, caused either by genetic or epigenetic loss of the receptor, such as ER promoter B associated factor 1.8 Thus, clarifying the extent of within-patient heterogeneity of ER expression is critically important for treatment decision making.
Positron emission tomography (PET) with ER-targeting radiopharmaceuticals is a noninvasive method for assessing regional ER expression in vivo. Several studies have shown that fluorine-18 (18F) fluoroestradiol (FES) PET can reliably detect ER+ tumor lesions and that 18F-FES uptake correlates well with immunohistochemical scoring for ER.9, 10, 11 Furthermore, low 18F-FES uptake was a strong predictor for failure of antihormonal therapy.12 The advantages of in vivo assessment of ERs include avoiding sampling error and assessing the entire tumor volume receptor status rather than part of the tumor, and assessing the biologic activity of the receptor at diagnosis and in response to treatment.13 Based on the advantages mentioned above, our study was to investigate the within-patient and between-patient heterogeneity of ER expression among tumor sites by using 18F-FES PET–computed tomography (CT) imaging.
Section snippets
Patient Selection
From June 2010 to December 2011, 32 breast cancer patients underwent both 18F-FES and 18F-FDG PET-CTs in our center. The patients were enrolled through one of several protocols: by predicting response to endocrine treatment, the correlation of FES uptake to an in vitro assay of ER, and by using 18F-FES PET-CT as a diagnostic tool for the patients presenting with a clinical dilemma. Concomitant bisphosphonate therapy or trastuzumab was not an exclusionary criterion but concurrent cytotoxic
Patient Characteristics
The characteristics of the 32 18F-FES PET-CT studies analyzed for 32 breast cancer patients are summarized in Table 1. All the patients were women. Among them, 8 patients were initial ones, which meant that they did not have any treatment before the scans. The remaining 24 patients had recurrent or metastatic breast cancers after operations and adjuvant treatments.
The Quality Control of 18F-FES
The radiochemical purity of 18F-FES prepared by us was > 98%. Specific activity was available for 32 scans, with a mean of 137,936
Discussion
Breast cancer is a heterogeneous disease, and there is a continual drive to identify markers that will aid in predicting prognosis and response to therapy. To date, relatively few markers have established prognostic power. Among them, ER is probably the most powerful predictive marker in breast cancer management, both in determining prognosis and in predicting response to hormone therapies.17 ER expression is routinely measured in clinical practice by in vitro assay of biopsy material. Although
Conclusion
18F-FES uptake and 18F-FDG uptake varied greatly both within and among patients. 18F-FES PET-CT demonstrated a conspicuous number of patients with the heterogeneity of ER expression. Because clarifying ER status in advanced breast cancer is crucial for treatment decision making, 18F-FES PET-CT is particularly promising in the metastatic setting in which patients have widespread lesions, especially bone lesions, which are difficult to biopsy.
Disclosure
The authors have stated that they have no conflicts of interest.
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Imaging of Bone Metastases in Breast Cancer
2022, Seminars in Nuclear MedicineCitation Excerpt :Patients with a low ratio had a worse prognosis.60 Further studies of 18F-FES in metastatic breast cancer noted heterogeneity between different metastatic sites, with bone metastases showing higher uptake than lymph node or lung metastases,61 and significant heterogeneity within and between individual patients.62 68Ga-FAPI tracers have shown high uptake in a variety of different tumors and there is also some early evidence that this tracer may be beneficial in breast cancer with primary tumors as well as metastases at most metastatic sites (including bone) showing higher uptake and sensitivity compared to 18F-FDG.63,64
FES-PET and breast carcinomas: Current situation in 2021
2021, Medecine NucleairePET imaging of breast cancer: Role in patient management
2015, PET ClinicsCitation Excerpt :Typically, a significantly greater tumor SUV is noted in responders compared with nonresponders. However, patients with tumors that bind and concentrate estrogen do not uniformly respond or benefit from treatment—this may be linked to the heterogenous distribution and ER expression.96 FES demonstrates intrapatient and interpatient variability of uptake and ER expression80 and can be of prognostic value.
16α-[<sup>18</sup>F]-fluoro-17ß-oestradiol ([<sup>18</sup>F]FES): A biomarker for imaging oestrogen receptor expression with positron emission tomography (PET)
2015, Medecine NucleaireCitation Excerpt :18F]FES also helped in the identification of metastatic sites in a preoperative setting. In the metastatic setting, [18F]FES can demonstrate the heterogeneity of ER expression in the same patient, namely ER status of bone metastases [35]. [18F]FES-PET uterine accumulation is affected by endocrine therapy, as it has been shown in two tamoxifen-treated postmenopausal patients in whom endometrial hyperplasia lesions were [18F]FES-negative, while they should be [18F]FES-avid lesions [36].
Head-to-head comparison of <sup>18</sup>F-FDG and <sup>18</sup>F-FES PET/CT for initial staging of ER-positive breast cancer patients
2023, European Journal of Hybrid Imaging
Zhongyi Yang and Yifei Sun contributed equally to the paper.