Abstract OT1-06-04: [18F] fluoroestradiol (FES) PET as a predictive measure for endocrine therapy in women with newly diagnosed metastatic breast cancer
Authors: Linden H , Clark A , Fowler A , Novakova A , Mankoff D , Dehdashti F 
Published: February 2018

Background: The majority of metastatic breast cancer patients have estrogen-receptor positive (ER+) disease. Therapy options include cytotoxic chemotherapy and ER-directed therapy, including endocrine therapy with or without molecularly targeted agents such as CK4/6 inhibitors. ER-targeted therapy is most commonly given first-line due to improved tolerability. However, not all patients will respond to first-line endocrine therapy due to intrinsic endocrine-therapy resistance mechanisms as well as tumor heterogeneity. There are no current methods in standard practice to inform on either of these issues.

F-18 fluorestradiol (FES), an estrogen analogue has been considered the most promising ER imaging agent and is widely studied in breast cancer. FES positron emission tomography (PET) evaluates multiple tumor sites simultaneously and, thus, can inform on tumor heterogeneity of ER expression, and can measure ER binding in primary and metastatic sites (e.g., lymph nodes, lung, bone, and soft tissue). Like tissue ER expression, FES positivity, as measured by standardized uptake value (SUV), has been shown to predict response to endocrine therapy with selective ER modulators or aromatase inhibitors in first-line therapy or salvage settings in small studies. Typically, a significantly higher tumor SUV was noted in responders compared with non-responders. Since FES uptake can provide a better assessment of ER expression across all sites of metastatic disease, FES may provide more expansive information on ER expression.. Furthermore, preliminary studies examining FES-PET in metastatic breast cancer have suggested that baseline FES uptake may predict response to endocrine therapy.

Trial Design: This is a prospective trial for patients about to start first line endocrine therapy for advanced ER+ breast cancer. Participants will undergo an FDG-PET within six weeks of FES-PET. FES-PET and serum hormone level to be completed prior to endocrine therapy. Patients may opt to have a 2nd FES-PET for test-re-test of FES-PET.

Specific Aims: Primary Aim : To assess the relationship between ER expression measured by FES-PET/CT and clinical benefit (response plus stable disease) of newly diagnosed ER+ metastatic breast cancer to endocrine therapy.

Secondary Aim: To assess the correlation between FES uptake in ER+ metastatic breast cancer and tissue ER expression.

Eligibility: Patients must have confirmed ER+ HER2- metastatic breast cancer and planning to receive endocrine therapy with or without CK 4/6 inhibitors. Patient must NOT have a history of &gt;1 line of administered chemotherapy for metastatic disease and may not have received endocrine therapy for advanced disease. Prior endocrine or chemotherapy in the adjuvant setting is allowed.

Methods: Participants will undergo a F-18 fluorodeoxyglucose (FDG)-PET/CT within six weeks of FES-PET/CT. FES-PET/CT will be completed prior to treatment initiation. Patients may opt to have a 2nd FES-PET for test-re-test of FES-PET/CT

Present and Target Accrual: A total of 13 out of 99 patients have been enrolled onto this imaging study.

Citation Format: Linden H, Clark A, Fowler A, Novakova A, Mankoff D, Dehdashti F. [18F] fluoroestradiol (FES) PET as a predictive measure for endocrine therapy in women with newly diagnosed metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-04.