Dataset Information

Analyzing the Estrogen Receptor Status of Liver Metastases with [¹⁸F]-FES-PET in Patients with Breast Cancer.

ABSTRACT:

Background

Positron emission tomography (PET) with 16α-[¹⁸F]-fluoro-17β-estradiol ([¹⁸F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [¹⁸F]-FES uptake. We evaluated whether [¹⁸F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard.

Methods

Patients with metastatic breast cancer (n = 23) were included if they had undergone a [¹⁸F]-FES-PET, liver metastasis biopsy, CT-scan, and [¹⁸F]-FDG-PET. [¹⁸F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined.

Results

Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER- metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive.

Conclusion

In the majority of liver metastases, ER status can be determined with [¹⁸F]-FES-PET if background correction and separate thresholds are applied.

SUBMITTER: Boers J

PROVIDER: S-EPMC8617814 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16?-18F-fluoro-17?-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). METHODS:Eligible patients were postmenopausal women with ER+, HER2- ABC; tumor progression after ??6?months of 1-3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400?mg elacestrant once daily (QD) and one treated with 200?mg elacestrant QD with dose escalation to 400?mg QD after 14?days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4?h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14?days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. RESULTS:Patients (n?=?16; median age, 53.5?years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400?mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400?mg). Residual ER availability (>?25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400?mg (3/78, 37.5%) and 1 patient receiving 400?mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in >?20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. CONCLUSION:Elacestrant 200?mg and 400?mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016.

Project description:PET imaging is useful for evaluating locally advanced primary breast cancer. Expression of specific molecular markers in these cancers, such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status, has direct prognostic and therapeutic implications in patient management. This study aimed to determine whether a relationship exists between tumor glucose use and important molecular markers in invasive breast cancer. For our purposes, tumor glucose use is quantified by the PET-derived parameter maximum standardized uptake value (SUV).Breast tumors from 36 patients were excised and examined histologically after PET. ER, PR, and HER2 status were determined for all lesions histopathologically. In addition, genomewide expression for a subset of 20 tumors was analyzed using the human genome U133A oligonucleotide microarray.A significant association was found between estrogen ER status and lesion SUV. ER-negative tumors (n = 17; median SUV, 8.5) demonstrated a significantly higher maximum SUV than did ER-positive tumors (n = 19; median SUV, 4.0) (P < 0.001). No significant association existed between SUV and PR status, HER2/neu status, lymph node involvement, or tumor size. Unsupervised hierarchic clustering of the 20 genetically profiled cancers segregated tumor samples into 2 primary groups of 10 patients each, largely corresponding to ER status.In locally invasive primary breast cancer, ER-negative tumors display higher (18)F-FDG uptake than ER-positive tumors. Microarray analysis confirms these data and identifies genes associated with increased glucose use as measured by PET. These genes significantly overlap those of a previously validated ER-status molecular phenotype. These preliminary data support a growing body of evidence that ER-positive and ER-negative breast cancers have distinct disease-specific patterns. Further validation prospectively and with larger numbers will be required to establish a robust molecular signature for metabolic uptake and patterns of aggressive behavior in advanced breast cancer.

Project description:PURPOSE:Correct identification of tumour receptor status is important for treatment decisions in breast cancer. [18F]FES PET and [18F]FDHT PET allow non-invasive assessment of the oestrogen (ER) and androgen receptor (AR) status of individual lesions within a patient. Despite standardised analysis techniques, interobserver variability can significantly affect the interpretation of PET results and thus clinical applicability. The purpose of this study was to determine visual and quantitative interobserver variability of [18F]FES PET and [18F]FDHT PET interpretation in patients with metastatic breast cancer. METHODS:In this prospective, two-centre study, patients with ER-positive metastatic breast cancer underwent both [18F]FES and [18F]FDHT PET/CT. In total, 120 lesions were identified in 10 patients with either conventional imaging (bone scan or lesions > 1?cm on high-resolution CT, n = 69) or only with [18F]FES and [18F]FDHT PET (n = 51). All lesions were scored visually and quantitatively by two independent observers. A visually PET-positive lesion was defined as uptake above background. For quantification, we used standardised uptake values (SUV): SUVmax, SUVpeak and SUVmean. RESULTS:Visual analysis showed an absolute positive and negative interobserver agreement for [18F]FES PET of 84% and 83%, respectively (kappa = 0.67, 95% CI 0.48-0.87), and 49% and 74% for [18F]FDHT PET, respectively (kappa = 0.23, 95% CI - 0.04-0.49). Intraclass correlation coefficients (ICC) for quantification of SUVmax, SUVpeak and SUVmean were 0.98 (95% CI 0.96-0.98), 0.97 (95% CI 0.96-0.98) and 0.89 (95% CI 0.83-0.92) for [18F]FES, and 0.78 (95% CI 0.66-0.85), 0.76 (95% CI 0.63-0.84) and 0.75 (95% CI 0.62-0.84) for [18F]FDHT, respectively. CONCLUSION:Visual and quantitative evaluation of [18F]FES PET showed high interobserver agreement. These results support the use of [18F]FES PET in clinical practice. In contrast, visual agreement for [18F]FDHT PET was relatively low due to low tumour-background ratios, but quantitative agreement was good. This underscores the relevance of quantitative analysis of [18F]FDHT PET in breast cancer. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01988324. Registered 20 November 2013, https://clinicaltrials.gov/ct2/show/NCT01988324?term=FDHT+PET&draw=1&rank=2.

Project description:Purpose To determine the binding specificity of 18F-16?-17?-fluoroestradiol (FES) in estrogen receptor (ER) ?-positive breast cancer cells and tumor xenografts. Materials and Methods Protocols were approved by the office of biologic safety and institutional animal care and use committee. By using ER-negative MDA-MB-231 breast cancer cells, clonal lines were created that expressed either wild-type (WT; 231 WT ER) or G521R mutant ER? (231 G521R ER), which is defective in estradiol binding. ER? protein levels, subcellular localization, and transcriptional function were confirmed. FES binding was measured by using an in vitro cell uptake assay. In vivo FES uptake was measured in tumor xenografts by using small-animal positron emission tomographic/computed tomographic imaging of 24 mice (17 WT ER tumors, nine mutant G521R ER tumors, eight MDA-MB-231 tumors, and four MCF-7 ER-positive tumors). Statistical significance was determined by using Mann-Whitney (Wilcoxon rank sum) test. Results ER? transcriptional function was abolished in the mutated 231 G521R ER cells despite appropriate receptor protein expression and nuclear localization. In vitro FES binding in the 231 G521R ER cells was reduced to that observed in the parental cells. Similarly, there was no significant FES uptake in the 231 G521R ER xenografts (percent injected dose [ID] per gram, 0.49 ± 0.042), which was similar to the negative control MDA-MB-231 xenografts (percent ID per gram, 0.42 ± 0.051; P = .20) and nonspecific muscle uptake (percent ID per gram, 0.41 ± 0.0095; P = .06). Conclusion This study showed that FES retention in ER-positive breast cancer is strictly dependent on an intact receptor ligand-binding pocket and that FES binds to ER? with high specificity. These results support the utility of FES imaging for assessing tumor heterogeneity by localizing immunohistochemically ER-positive metastases that lack receptor-binding functionality. © RSNA, 2017 Online supplemental material is available for this article.

Dataset Information

Analyzing the Estrogen Receptor Status of Liver Metastases with [¹⁸F]-FES-PET in Patients with Breast Cancer.

Background

Methods

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Analyzing the Estrogen Receptor Status of Liver Metastases with [18F]-FES-PET in Patients with Breast Cancer.

Background

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Analyzing the Estrogen Receptor Status of Liver Metastases with [¹⁸F]-FES-PET in Patients with Breast Cancer.