Assessment of Functional Status of Estrogen Receptors in Breast Cancer by Positron Emission Tomography
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: 18F-FFNP; CTI/Siemens Biograph 40 PET/CT Scanner; Estradiol; 18F-FDG
Intervention description: Will include (1) 18-FDG-PET/CT scan
Will include (2) 18F-FFNP-PET/CT scans
Intervention MeSH terms: Estradiol
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the uptake of a radioactive tracer
      21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (FFNP)
      uptake, which binds to breast cancer progesterone receptors (PgRs) on a PET/CT scan before
      and after administration of estradiol for one day (estrogen challenge) to determine if the
      change in uptake is a predictor of response to endocrine therapy (ET) in patients with
      hormone-sensitive estrogen receptor positive (ER+), human epidermal growth factor receptor
      2-negative (HER2-) breast cancer. Estradiol is the most potent of the naturally occurring
      estrogens, and can be administered to treat menopausal symptoms and also sometimes to treat
      metastatic breast cancer. The investigators propose to study patients with biopsy-proven
      newly diagnosed, locally advanced, metastatic, or recurrent breast cancer who are going to be
      treated with endocrine therapy (ET) (tamoxifen,aromatase inhibitors or fulvestrant as
      standard of care therapy.

      Subjects will undergo a total of two FFNP-PET/CT scans; one before and a second one
      immediately following the one day estradiol challenge before the start of standard of care
      ET. The estradiol challenge will consist of administering a total of 6 mg of estradiol orally
      (three doses of 2 mg each) given at approximately 8 hour intervals and over a 24 hour period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must be postmenopausal defined as meeting one or more of the following:

               -  Age ≥ 60 years

               -  Amenorrheic for at least 12 months

               -  Surgically sterile- having undergone bilateral oophorectomy,

               -  FSH level in postmenopausal range according to institutional standards (note
                  follicle-stimulating hormone (FSH) laboratory testing must be ordered as standard
                  of care to determine optimal treatment and should not be ordered simply to
                  confirm eligibility to this study)

               -  OR Pre-menopausal for whom standard estradiol treatment (ET) is planned with
                  ovarian suppression (imaging on study should be completed prior to start of
                  ovarian suppression)

          -  Patient must have histological or cytological confirmed breast cancer and fall into
             one of the following categories:

               -  New diagnosis with plans for at least 6 months of neoadjuvant ET or any amount of
                  neoadjuvant ET if surgery is planned as this will be used for response assessment
                  .

               -  Patients with newly diagnosed metastatic breast cancer or patient with known
                  metastatic disease who has progressed while on therapy (no washout period is
                  needed if the patient was treated with AIs or chemotherapy, but 2 months washout
                  period is needed if the patient was treated with tamoxifen) who are going to be
                  treated with ET.

          -  Patient must have any one of the following types of breast cancer (primary or
             metastatic): ER+/PgR+/HER2- or ER+/PgR-/HER2-.

               -  ER+ is defined as Allred score of at least 4 and greater.

               -  PgR+ is defined as Allred score of at least 4 and greater.

               -  Immunohistochemistry (IHC) is the primary assay methodology for HER2. HER2-
                  refers to HER2 of 0, 1+ by IHC or negative by fluorescence in situ hybridization
                  (FISH)

          -  Patient must have at least one measurable lesion according to RECIST 1.1 by
             radiological evaluation (ultrasound, mammography, MRI, CT, PET) or physical
             examination.

               -  Patients with evaluable osseous metastasis that are lytic or mixed
                  lytic-sclerotic are eligible.

               -  Patients with hepatic lesions may be eligible provided the location of the lesion
                  is peripheral or not too close to hepatic ducts. Decision on hepatic lesion
                  eligibility will be made by the principal investigator or sub-investigator after
                  careful review of all available imaging to ensure evaluation of the lesion will
                  not be obscured by normal hepatobiliary excretion of 18F-FFNP.

          -  Patient must be able to understand and willing to sign a written informed consent
             document.

          -  Prior chemotherapy or endocrine therapy is allowed

          -  The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
             of 0-2 or, based on the judgment of the treating medical oncologist, can tolerate
             imaging and at least 6 months of ET

          -  The patient should have a life expectancy of > 6 months.

        Exclusion Criteria:

          -  Patient with other invasive malignancies, with the exception of non-melanoma skin
             cancer or cervical carcinoma in-situ, who had (or have) any evidence of the other
             cancer present within the last 5 years

          -  Unable to tolerate up to 60 min of PET imaging per imaging session.

          -  Patients with non-measurable non-evaluable lesions such as pleural effusion are not
             eligible to participate.

          -  Patients with vertebral lesions that, in the opinion of the Principal Investigator and
             the treating medical oncologist, pose an imminent risk for cord compression.