18F FES-PET/MRI for Tailoring Treatment of Luminal A and Lobular Breast Cancer

Study Overview
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Brief Summary
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Study hypothesis is that combining the advantages of hybrid PET/MRI and the high sensitivity/specificity of 16-alpha-18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of estrogen binding to functionally active ER, the investigators could obtain a reliable, non-invasive, operator-independent, one-stage imaging method for staging LumA and ER-positive Lobular tumours.

Detailed Description
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This is a single-centre prospective cohort study where patients with LumA and ER-positive Lob will be enrolled in 4 cohorts undergoing: primary surgery; induction endocrine therapy; neoadjuvant chemotherapy; systemic therapy for metastatic disease. For the purpose of the study an additional FES PET/MRI exam will be performed at baseline for local and systemic staging and a second exam after systemic therapy. Correlations between FES PET/MRI parameters and pathology, gene expression and FDG PET parameters, when available, will be investigated. Aim 1: Evaluating the performance of FES PET/MRI in axillary staging compared with axillary surgery. Aim 2: Evaluating potential correlations between changes in FES uptake and changes in proliferation index after 3 weeks of endocrine therapy before surgery. Aim 3: Evaluating the performance of FES PET/MRI in staging of patients undergoing systemic therapy in comparison with standard imaging. Additionally, biological determinants of tumor heterogeneity will be investigated.

Official Title
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18F-FES PET/MRI for Tailoring Treatment of Luminal A and Lobular Breast Cancer: a Phase II Prospective Cohort Study Evaluating the Performance of FES PET/MRI in Axillary Staging Compared With Axillary Surgery

Conditions
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Breast Cancer Female, Lobular Breast Carcinoma, PET/MRI, Axillary Lymphadenopathy, Luminal A Breast Cancer

Intervention / Treatment
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* Drug: FES
* Procedure: PET/MRI A
* Procedure: PET/MRI B
* Procedure: PET/MRI C
* Procedure: PET/MRI D
* Genetic: Translational analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients, age>= 18 yrs, diagnosed with primary or advanced breast cancer LumA or ER-positive Lobular subtypes Cohort A candidates to surgery as first treatment regardless of cN ER-positive Her2 negative BC with ki67>10% Cohort B ER positive BC treated with induction ET Cohort C candidates to neoadjuvant chemotherapy Cohort D Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression Exclusion Criteria: ER-negative tumors Pregnancy; Contraindication to PET; Contraindication to MRI; Claustrophobia; Allergy to the MR contrast agent; Severe renal insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cohort A candidates to surgery as first treatment regardless of cN ER+ Her2 negative BC with ki67>10% Cohort B ER positive BC treated with induction ET Cohort C candidates to neoadjuvant chemotherapy Cohort D Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Candidates to surgery as first treatment regardless of cN ER+ Her2 negative BC with ki67>10% | Drug: FES<br>* 16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam<br>Procedure: PET/MRI A<br>* An additional FES PET/MRI will be performed before surgery.<br>Genetic: Translational analysis<br>* Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.<br>|
| Experimental: Cohort B<br>• ER positive BC treated with induction ET | Drug: FES<br>* 16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam<br>Procedure: PET/MRI B<br>* Two additional PET/MRI will be performed before and after induction ET.<br>Genetic: Translational analysis<br>* Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.<br>|
| Experimental: Cohort C<br>• Candidates to neoadjuvant chemotherapy | Drug: FES<br>* 16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam<br>Procedure: PET/MRI C<br>* Two additional PET/MRI will be performed before and after two cycles of neoadjuvant chemotherapy.<br>Genetic: Translational analysis<br>* Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.<br>|
| Experimental: Cohort D<br>• Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression | Drug: FES<br>* 16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam<br>Procedure: PET/MRI D<br>* Two additional PET/MRI will be performed before and after two cycles of systemic therapy.<br>Genetic: Translational analysis<br>* Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of FES PET/MRI in detecting macrometastatic axillary lymph nodes | Ability of FES PET/MRI to detect macrometastatic (tumor deposit>2mm) axillary lymph nodes in BC patients with LumA or Lob who are candidates to primary surgery. | Day 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Standard Uptake Value (SUV) of FES in patients undergoing induction Endocrine Treatment (ET) | To investigate the potential correlation between Δ(FES SUV) and Δ(Ki-67 as proliferation index) after induction ET in luminal BC. | Day 0 and Day 50 |