Elsevier

Clinical Breast Cancer

Volume 13, Issue 5, October 2013, Pages 359-363
Clinical Breast Cancer

Original study
Can Fluorine-18 Fluoroestradiol Positron Emission Tomography–Computed Tomography Demonstrate the Heterogeneity of Breast Cancer In Vivo?

https://doi.org/10.1016/j.clbc.2013.02.012Get rights and content

Abstract

Aim

Our study was to investigate the heterogeneity of estrogen receptor (ER) expression among tumor sites by using fluorine-18 (18F) fluoroestradiol (FES) positron-emission tomography–computed tomography (PET-CT) imaging.

Methods

Thirty-two breast cancer patients underwent both 18F-FES and 18F fluorodeoxyglucose (FDG) PET-CTs from June 2010 to December 2011 in our center (mean age, 53 years; range, 27-77 years). We used the maximum standardized uptake value to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER+ and ER. The difference of heterogeneity between the initial patients and patients with recurrent or metastatic disease after treatments was assessed by using the χ2 test. Also, the 18F-FES uptake was compared with the 18F-FDG uptake by use of Spearman correlation coefficients.

Results

A total number of 237 lesions in 32 patients were detected. Among them, most lesions (64.1% [152/237]) were bone metastasis. A striking 33.4-fold difference in 18F-FES uptake was observed among different patients (maximum standardized uptake value range, 0.5 to approximately 16.7), and a 8.2-fold difference was observed among lesions within the same individual (1.0 to approximately 8.2). As for 18F-FDG uptake, the difference was 11.6-fold (1.3 to approximately 15.1) and 9.9-fold (1.4 to approximately 13.8), respectively. In 28.1% (9/32) of the patients, both 18F-FES+ and 18F-FES metastases were present, which suggests partial discordant ER expression. After treatments, 37.5% (9/24) patients with recurrent or metastatic breast cancer showed heterogeneity, whereas no untreated patient was detected to exist discordant ER expression (χ2, 4.174; P < .05). In addition, the 18F-FES uptake showed a weak correlation with the 18F-FDG uptake (ρ = 0.248; P < .05).

Conclusion

18F-FES 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.

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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    Zhongyi Yang and Yifei Sun contributed equally to the paper.

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