Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET

A Gennari; E Brain; A De Censi; O Nanni; R Wuerstlein; A Frassoldati; J Cortes; V Rossi; M Palleschi; J L Alberini; F Matteucci; A Piccardo; G Sacchetti; H Ilhan; F D'Avanzo; B Ruffilli; S Nardin; M Monti; M Puntoni; V Fontana; L Boni; N Harbeck; ET-FES Collaborative Group

doi:10.1016/j.annonc.2024.02.007

Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with ¹⁸F-fluoroestradiol (¹⁸F-FES) CT/PET

Ann Oncol. 2024 Feb 28:S0923-7534(24)00057-7. doi: 10.1016/j.annonc.2024.02.007. Online ahead of print.

Authors

A Gennari¹, E Brain², A De Censi³, O Nanni⁴, R Wuerstlein⁵, A Frassoldati⁶, J Cortes⁷, V Rossi⁸, M Palleschi⁹, J L Alberini¹⁰, F Matteucci¹¹, A Piccardo¹², G Sacchetti¹³, H Ilhan¹⁴, F D'Avanzo⁸, B Ruffilli¹⁵, S Nardin¹⁶, M Monti⁴, M Puntoni¹⁷, V Fontana¹⁸, L Boni¹⁸, N Harbeck⁵; ET-FES Collaborative Group

Collaborators

ET-FES Collaborative Group:
Bianca Malagutti, Bassam Dib, Carmen Branni, Mauro D'Amico, Nicoletta Provinciali, Davide Corradengo, Francesco Fiz, Massimiliano Iacozzi, Andrea Rocca

Affiliations

¹ Department of Translational Medicine, University of Piemonte Orientale, Novara; Division of Medical Oncology, Maggiore University Hospital, Novara, Italy. Electronic address: alessandra.gennari@uniupo.it.
² Department of Medical Oncology, Institut Curie-Hôpital René Huguenin, Saint-Cloud, France.
³ Medical Oncology, E.O. Ospedali Galliera, Genova.
⁴ Biostatistics and Clinical Trials Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
⁵ Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany.
⁶ Clinical Oncology, S. Anna University Hospital, Ferrara, Italy.
⁷ International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona; Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.
⁸ Division of Medical Oncology, Maggiore University Hospital, Novara, Italy.
⁹ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
¹⁰ Nuclear Medicine Department Centre Georges-Francois Leclerc, Dijon Cedex, France.
¹¹ Nuclear Medicine Unit, IRCCS Istituto Romagnolo per lo studio dei tumori (IRST) -"Dino Amadori", Meldola.
¹² Department of Nuclear Medicine, E.O. Ospedali Galliera, Genoa.
¹³ Division of Nuclear Medicine Unit, Maggiore University Hospital, Novara, Italy.
¹⁴ Department of Nuclear Medicine, LMU University Hospital, Munich, Germany.
¹⁵ Department of Translational Medicine, University of Piemonte Orientale, Novara.
¹⁶ Medical Oncology Unit 1, IRCCS-Ospedale Policlinico San Martino, Genoa.
¹⁷ Clinical and Epidemiological Research Unit, University Hospital of Parma, Parma.
¹⁸ Department of Clinical Epidemiology, IRCSS Ospedale Policlinico San Martino, Genoa, Italy.

PMID: 38423389
DOI: 10.1016/j.annonc.2024.02.007

Abstract

Background: ¹⁸F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated ¹⁸F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC).

Patients and methods: Eligible patients underwent an ¹⁸F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with ¹⁸F-FES SUV < 2.

Results: Overall, 147 patients were enrolled; 117 presented with ¹⁸F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005).

Conclusions: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on ¹⁸F-FES CT/PET SUV.

Keywords: (18)F-fluoroestradiol PET/CT; endocrine sensitivity; molecular imaging; randomized clinical trial; standardized uptake value (SUV).