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

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

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.

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.

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

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

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

Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.

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.

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.

FES PET/MRI sensitivity compared to that of standard imaging in patients undergoimg systemic therapy for neoadjuvant purposes or for metastatic disease.

Results from FES PET/MRI will be compared with those from standard imaging in terms of sensitivity and number of lesions detected.

Results of FES PET/MRI after two cycles of therapy will be compared to final pathology (cohort C) or standard imaging at 6 months (cohort D)

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

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