Title
Integrating Minimally Invasive Biomarkers of Estrogen Signaling to Detect Endocrine Therapy Resistance in Metastatic Invasive Lobular Breast Cancer

Description
This pilot observational study is being done to identify possible biomarkers of response to endocrine therapy in patients with ER/PR+ metastatic lobular breast cancer (LBC) starting new endocrine therapy. 18F-fluorofuranylnorprogesterone Positron Emission Tomography/Computed Tomography (FFNP-PET/CT) and liquid biopsies will be performed at baseline and after 4 weeks of treatment. Baseline levels and dynamic on-treatment changes in estrogen signaling as measured by FFNP-PET/CT and circulating tumor cell (CTC) liquid biopsy will be correlated with clinical response to endocrine therapy and progression-free survival in the above cohort of patients.

Objective
Primary Objectives:
1. To define the dynamics of FFNP-PET/CT in response to endocrine therapy in ER/PR+ metastatic LBC.
2. To define the dynamics of CTC estrogen signaling and circulating tumor DNA in response to endocrine therapy in ER/PR+ metastatic LBC.

Secondary Objectives:
1. To correlate baseline and on treatment FFNP-PET/CT and CTC estrogen signaling with clinical response to endocrine therapy in ER/PR+ metastatic LBC.
2. To evaluate the safety of FFNP infusion in patients with ER/PR+ metastatic LBC.

Treatment Experimental: Participants with ER/PR+ metastatic lobular breast cancer (LBC)

Drug: 18F-fluorofuranylnorprogesterone
The dose of the investigational imaging agent, FFNP, is approximately 7 millicurie (mCi) (259 megabecquerels (MBq)), IV slow infusion over approximately two minutes followed by saline flush.
Other Name: FFNP

Device: Liquid Biopsy
15ml of whole blood will be collected into two Ethylenediaminetetraacetic acid (EDTA) tubes at each timepoint, CTCs are isolated using the microfluidic Versatile Exclusion-based Rare Sample Analysis (VERSA) platform that integrates CTC capture with RNA extraction on a single chip using Exclusion-Based Sample Preparation (ESP) technology
Other Name: Circulating Tumor Cells (CTC)

Device: Positron Emission Tomography/Computed Tomography
FFNP drug in combination with PET/CT scans to image participant
Other Name: PET/CT

Key Eligibility Inclusion Criteria:

Willing to provide informed consent

Individuals at least 18 years of age

Have biopsy-proven ER/PR-positive (defined as ER >/=1 percent and PR >/=1 percent by IHC) and HER2-negative advanced or metastatic LBC starting new standard of care endocrine therapy

Adequate organ function as indicated by standard laboratory tests (CBC, liver function tests or CMP) allowing for systemic breast cancer treatment per treating oncologist

Patients with evaluable bone-only disease that is lytic or mixed lytic-sclerotic are eligible

Willing to comply with all study procedures and be available for the duration of the study

Disease may be measurable by RECIST 1.1 criteria or non-measurable. Lesion size must be at least 1cm. If only bone lesions present, they should be lytic or mixed lytic-sclerotic. If only liver lesions present, patient is not eligible.

Patients with active brain metastases

Patients with liver-only disease are not eligible due to high background liver activity related to the radiopharmaceutical's hepatobiliary route of elimination

Unable to lie flat during or tolerate PET/CT

Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP

Presence of liver failure as judged by patient's treating physician

Individuals who are pregnant, lactating, or planning on becoming pregnant during the study

Not suitable for study participation due to other reasons at the discretion of the investigators

Patients with progesterone-receptor negative disease defined as PR <1 percent by IHC

Applicable Disease Sites
Breast

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital