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Comparison of Diagnostic Sensitivity of [18F]Fluoroestradiol

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Comparison of Diagnostic Sensitivity of [18F]Fluoroestradiol Chae et al. EJNMMI Research (2020) 10:54 https://doi.org/10.1186/s13550-020-00643-z ORIGINAL RESEARCH Open Access Comparison of diagnostic sensitivity of [18F]fluoroestradiol and [18F]fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer Sun Young Chae1, Hye Joo Son1, Dong Yun Lee1, Eonwoo Shin1, Jungsu S. Oh1, Seung Yeon Seo1, Sora Baek2, Ji Young Kim3, Sae Jung Na4 and Dae Hyuk Moon1* Abstract Background: To compare the diagnostic sensitivity of [18F]fluoroestradiol ([18F]FES) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer. Methods: Our database of consecutive patients enrolled in a previous prospective cohort study to assess [18F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [18F]FDG PET/CT. The sensitivity of qualitative [18F]FES and [18F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses. Results: Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [18F]FES PET/CT was 71.1% (32/45, 95% CI, 55.7–83.6), while that of [18F]FDG PET/CT was 80.0% (36/45, 95% CI, 65.4–90.4) with a threshold of positive interpretation, and 93.3% (42/ 45, 95% CI, 81.7–98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [18F]FES and [18F]FDG PET/CT (P = 0.48) with a threshold of positive [18F]FDG uptake, but the sensitivity of [18F]FDG was significantly higher than [18F]FES (P = 0.013) with a threshold of equivocal [18F]FDG uptake. One patient with a benign lesion showed negative [18F]FES but positive [18F]FDG uptake. (Continued on next page) * Correspondence: [email protected] 1Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Chae et al. EJNMMI Research (2020) 10:54 Page 2 of 9 (Continued from previous page) Conclusions: The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [18F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious. Keyword: Breast cancer, Estrogen receptor, [18F]FES PET/CT, [18F]FDG PET/CT Background PET/CT with [18F]fluoroestradiol ([18F]FES) provides a Breast cancer is one of the most frequently diagnosed can- unique method to noninvasively assess molecular infor- cers and is the leading cause of cancer death in women mation on ER expression [23, 24]. The diagnostic sensitiv- [1]. About 75% of all breast cancer expresses estrogen re- ity of [18F]FES PET/CT for the assessment of ER status in ceptor (ER) at the time of initial diagnosis [2]. The 20-year recurrent or metastatic lesions is good overall [25–31], risk of distant recurrence after adjuvant endocrine therapy which indicates a high sensitivity for diagnosing recurrent for ER-positive breast cancer ranges from 10 to 40% [3]. breast cancer in patients with a history of ER-positive The diagnosis of recurrence and restaging are important primary breast cancer. Of particular importance is the for determining appropriate treatment [4]. very high specificity of [18F]FES PET/CT [25–31], with no Current guidelines on breast cancer recommend that the false-positives having been reported in qualitative [18F]FES staging evaluation of women who present with recurrent studies. Therefore, [18F]FES PET/CT can be used as an breast cancer includes standard imaging studies [5, 6]. Posi- alternative to tissue biopsy and ER assays [31]andmay tron emission tomography/computed tomography (PET/ improve clinical decision-making when conventional CT) with [18F]fluorodeoxyglucose ([18F]FDG) would only work-up is inconclusive [32]. To our knowledge, the use be used in situations where standard staging studies are of [18F]FES PET/CT in the diagnosis of recurrent breast equivocal or suspicious [5, 6]. Although clinical studies have cancer in comparison with [18F]FDG PET/CT has not so indicated high diagnostic accuracy with sensitivities ranging far been studied. from 81 to 100% and specificities ranging from 52 to 91% Recently, we conducted a prospective cohort study to and have suggested the superiority of [18F]FDG PET/CT assess the diagnostic accuracy of [18F]FES PET/CT for over standard imaging studies [7–11], these studies are ER status in recurrent lesions in patients with breast largely retrospective with heterogeneous cohorts, and there cancer [31]. The included participants were a consecu- are also methodological issues of concern [7, 10, 11]. The tive series of all patients presenting with symptoms and diagnostic accuracy was not separately determined in pa- imaging findings of recurrent breast cancer with histo- tients who presented with equivocal or suspicious imaging logical confirmation of recurrent lesions. Most partici- studies [8, 12–14]. In addition, both false-negative and pants underwent [18F]FDG PET/CT for clinical reasons. false-positive [18F]FDG PET/CT results [7, 10]areinherent The direct comparison of [18F]FDG and [18F]FES PET/ in [18F]FDG PET/CT [15, 16]. The consensus is that biopsy CT in the same population is robust, as differences in is more likely to provide useful information [6]. Moreover, potential modifiers associated with the population, study the reference standard used in previous studies has ranged methods, and technologies can be eliminated. In the from histopathological diagnosis to clinical or radiological current study, we aimed to compare the diagnostic sensi- follow-up, and misclassification of disease might have led to tivity of [18F]FDG and [18F]FES PET/CT for breast cancer positive or negative biases. Finally, the positivity threshold recurrence in patients with ER-positive primary breast of [18F]FDG PET/CT may differ between studies, depend- cancer who were enrolled in a previous cohort study. ing on how to determine the foci of increased [18F]FDG up- take are related to benign conditions. Equivocal decisions Materials and methods arethereforelikelytobeinevitable[8, 9, 11, 12, 17–19]. Study design The histological and biological characteristics of The study patients were identified from our database of breast cancer have an important impact on tumor a prospective patient cohort who underwent [18F]FES visualization with [18F]FDG PET/CT [20]. [18F]FDG PET/CT for the assessment of ER status because of uptake correlates with histologic grade and tumor pro- recurrent or metastatic breast cancer lesions [31]. The liferation index [15, 21, 22], and [18F]FDG uptake is patients’ medical histories and [18F]FDG PET/CT studies higher in ER-negative tumors [15]. Accordingly, the performed to identify unsuspected regional nodal disease relatively lower [18F]FDG uptake in ER-positive breast and/or distant metastases were retrospectively reviewed. cancer may affect the diagnostic accuracy. To date, the Our institutional review board approved this study accuracy of [18F]FDG PET/CT for the diagnosis of re- protocol and waived the requirement for informed con- current breast cancer has not been separately reported sent. This study was conducted in accordance with the in patients with ER-positive primary breast cancer. Declaration of Helsinki and our institutional guidelines. Chae et al. EJNMMI Research (2020) 10:54 Page 3 of 9 Patients additional non-reference lesions in the order of highest All eligible patients had ER-positive primary breast can- intensity relative to background activity [25, 37]. Lesions cer with suspected first recurrence at presentation, were were interpreted as ER-positive breast cancer when the enrolled in a previous prospective cohort study to assess majority of [18F]FES assessments were positive. [18F]FES PET/CT, and underwent [18F]FDG PET/CT Two board-certified nuclear medicine physicians (H.J.S. within 60 days before needle biopsy or surgery. Patients and D.Y.L.) interpreted the [18F]FDG PET/CT images in were excluded if they had ER-negative or ER-unknown consensus using a syngo.via image display system (VB20A, primary breast cancer. The complete selection criteria, Siemens Healthineers), with the images displayed in a ran- setting, location, and dates of the prospective cohort dom sequence. These two physicians were also blinded to study were previously reported [31]. The patient popula- all patient information and the [18F]FES PET/CT images; tion used in this study represented a consecutive sample they only had knowledge of the location of the biopsy sites of eligible patients.
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