Non-invasive estrogen receptor assessment by [F-18]-fluorestradiol(FES)-PET or circulating tumor cells predicts receptor status in patients with metastatic breast cancer

Introduction: Estrogen receptor (ER) expression largely determines the therapy choice for patients diagnosed with metastatic breast cancer (MBC). Given potential conversion of ER-status, the current golden standard for ER assessment is by immunohistochemistry (IHC) on metastatic tissue. Since a biopsy is cumbersome and sometimes not feasible, ER-status assessments by means of [18F]-fluorestradiol (FES)-PET or circulating tumor cells (CTCs) might be potential alternatives. We hypothesize that FES-PET or CTCs can determine ER status in patients with MBC, in a more efficient and patient friendly way than IHC. Methods: In the Dutch multicenter IMPACT-MBC trial (NCT01832051) patients with non-rapidly progressive MBC at first presentation, regardless of subtype, underwent extensive molecular imaging (including FES-PET, 89Zr-trastuzumab-PET and serial [18F]-fluorodeoxyglucose (FDG)-PET), a metastasis biopsy and blood sampling to obtain a whole body molecular profile of their disease. ER-status on the metastasis biopsy was evaluated by IHC and considered positive if ≥10% of the tumor cells showed ER expression. The FES-PET was considered positive when the maximum standardized uptake value (SUVmax) of at least one lesion was ≥ 1.5. Reverse transcription polymerase chain reaction was used to quantify the ESR1 expression in CTCs. ER-positivity was defined as an ESR1 mRNA ΔCq level ≥ -7.86, corrected for background healthy donor blood signal, only in samples with ≥5 CTCs/7.5ml and a sufficient mRNA signal of reference and epithelial genes. Sensitivity, specificity, positive and negative predictive values were calculated (PPV and NPV). Results: From 178 patients of 201 evaluable patients both metastasis IHC and FES-PET could be assessed. 129 of these 178 patients had an IHC ER positive metastasis (72%) and 133 patients had a positive FES-PET (75%). The PPV and NPV for IHC by FES-PET were 91% and 82%, respectively. From 54 of the 178 patients, blood samples contained sufficient CTCs for ESR1 analysis, allowing combined assessment of IHC, FES-PET and CTCs. ER positive CTCs were present in 45 patients (83%). Conclusion: In newly diagnosed patients with MBC, ER-status in metastatic lesions could be predicted by means of non-invasive FES-PET scan or CTCs. Prediction was most optimal with FES-PET compared to CTCs, and combining FES-PET with CTCs did not essentially improve this. Furthermore, CTCs were not detectable in most of these patients with non-rapidly progressive MBC, limiting their applicability for the present purpose. However, as CTC assessment is most patient friendly, CTCs might be considered as first step in determining MBC ER-status. If ER positive CTCs are detected, ER positive disease is very likely; if no- or ER negative CTCs are detected, MBC ER-status needs to be further assessed by means of tissue confirmation or FES-PET. Funding: Dutch Cancer Society grant RUG 2012-5565, project EMCR 16-8196 Citation Format: Eisses B, Angus L, van der Vegt B, Sieuwerts AM, Kraan J, Martens JW, Glaudemans AW, Brouwers AH, Hoekstra OS, Oyen W, Emmering J, Gerritse S, Menke-van der Houven van Oordt CW, Boon E, van Herpen CM, Jager A, Sleijfer S, de Vries EG, Schroder CP. Non-invasive estrogen receptor assessment by [18F]-fluorestradiol(FES)-PET or circulating tumor cells predicts receptor status in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-09.