Molecular imaging to identify patients with metastatic breast cancer who benefit from endocrine treatment combined with cyclin-dependent kinase inhibition

Autor: Erik F. J. de Vries, Andor W. J. M. Glaudemans, Clasina M Venema, Ed Schuuring, Carolina P. Schröder, Geke A. P. Hospers, Jorianne Boers, Sjoerd G. Elias, Thomas C. Kwee, John W.M. Martens
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Molecular Neuroscience and Ageing Research (MOLAR), Translational Immunology Groningen (TRIGR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Medical Oncology
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Cancer Research
Pyridines
Estrogen receptor
Kaplan-Meier Estimate
THERAPY
Piperazines
Breast cancer
0302 clinical medicine
Positron Emission Tomography Computed Tomography
Antineoplastic Combined Chemotherapy Protocols
Outcome Assessment
Health Care
Neoplasm Metastasis
Estradiol
medicine.diagnostic_test
Aromatase Inhibitors
Letrozole
Middle Aged
Metastatic breast cancer
Cyclin-Dependent Kinases
Receptors
Estrogen
Positron emission tomography
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
medicine.drug
Adult
Endocrine therapy
medicine.medical_specialty
Breast Neoplasms
Palbociclib
Young Adult
03 medical and health sciences
SDG 3 - Good Health and Well-being
Fluorodeoxyglucose F18
CDK inhibition
Internal medicine
FES-PET
medicine
Humans
Protein Kinase Inhibitors
Aged
Fulvestrant
business.industry
Biomarker
medicine.disease
ESTROGEN-RECEPTORS
PALBOCICLIB
030104 developmental biology
FULVESTRANT
Heterogeneity
business
Zdroj: European Journal of Cancer, 126, 11-20. ELSEVIER SCI LTD
European Journal of Cancer, 126, 11-20. Elsevier Ltd.
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2019.10.024
Popis: BACKGROUND: Adding cyclin-dependent kinase (CDK) inhibitor to endocrine treatment improves outcome in œstrogen receptor (ER) positive metastatic breast cancer, but identifying the subset of patients who benefit is challenging. Response is potentially associated with ER expression heterogeneity. This is because, unlike the primary tumour in the breast that is localized to the organ, the metastatic breast cancer has spread and continues to spread to distant locations in the body such as bones, lungs, liver, axial skeleton, even to the central nervous system like the brain, wherefrom obtaining biopsies are not easy, and also, the metastasised tissues are heterogeneous. Positron emission tomography (PET) with 16α-[18F]fluoro-17β-œstradiol (FES), briefly referred to as FES-PET, allows whole-body ER assessment. We explored whether FES-PET heterogeneity and FES uptake were related to letrozole and palbociclib outcome, in patients with ER positive, metastatic breast cancer.PATIENTS AND METHODS: Patients underwent a baseline FES-PET and 18F-fluorodeoxyglucose (FDG) PET, the FDG-PET served to help identify active sites of breast cancer with contrast-enhanced computed tomography (CT). FES-PET heterogeneity score (% FES positive lesions divided by all lesions on FDG-PET and/or CT) and FES uptake were related to outcome and 8-week FDG-PET response. Circulating tumour DNA (CtDNA) samples for ESR1 mutation analysis were collected at baseline.RESULTS: In 30 patients with 864 metastatic lesions, baseline FES-PET heterogeneity was assessed. In 27 patients with 688 lesions, response was evaluated. Median time to progression (TTP) was 73 weeks (95% confidence interval [CI] 21 to ∞) in 7 patients with 100% FES positive disease, 27 weeks (14-49) in heterogeneous FES positive disease (20 patients), and 15 weeks (9 to ∞) without FES positivity (three patients; log-rank P = 0.30). Geometric mean FES uptake was 2.3 for metabolic progressive patients, 2.5 (Pvs progression = 0.82) for metabolic stable disease, and 3.3 (Pvs progression = 0.40) for metabolic response (Ptrend = 0.21). ESR1 mutations, found in 13/23 patients, were unrelated to FES uptake.CONCLUSION: This exploratory study suggests that FES-PET heterogeneity may potentially identify the subset of ER positive, metastatic breast cancer patients who benefit from letrozole combined with CDK inhibition.CLINICAL TRIAL INFORMATION: NCT02806050.
Databáze: OpenAIRE
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