A Pilot Study of FES Imaging to Optimize Tamoxifen Dose for Metastatic Breast Cancer Patients With ESR1 Mutations
Despite broad advancements in endocrine therapy for ERα+ breast cancer, resistance ultimately develops. A common driver of resistance are known ESR1 mutations that lead to constitutively active receptor signaling and transcriptional regulation that is always turned on despite the absence of estrogen. Patients with ESR1 mutations are expected to have decreased binding affinity for tamoxifen and thus may be underdosed on standard therapy. \[18F\]-fluoroestradiol Positron Emission Tomography/Computed tomography (FES-PET/CT) imaging is a novel functional imaging technique that can non-invasively measure ERα expression and inhibition in metastatic ERα+ breast cancer. The proposed a pilot study uses FES-PET/CT imaging to measure ERα blockade to determine the optimal dose of tamoxifen in patients with ESR1 mutations.
• Participants must have histologically confirmed breast cancer that is metastatic or unresectable with the following:
‣ Estrogen receptor expression by immunohistochemistry greater than or equal to 10%
⁃ ESR1 mutation identified using a Clinical Laboratory Improvement Amendments (CLIA) certified assay via tumor biopsy tissue or circulating free DNA (cfDNA)
⁃ human epidermal growth factor receptor 2 (HER2) negative
• Participants must have measurable disease as defined by RECIST 1.1 or evaluable bone disease with at least one lesion measuring 10 mm or greater in size. (Participants with bone and non-bone disease are eligible. One disease site must meet either the measurable or evaluable criteria outlined.) Participants with liver-only disease are not eligible due to the inherent hepatic uptake related to the radiopharmaceutical's hepatobiliary route of elimination.
• Participants must have received at least 1 prior line of endocrine therapy in the metastatic setting or have had progression within 12 months of adjuvant endocrine therapy. Prior Tamoxifen is allowed in any setting. Prior CDK4/6 in the metastatic setting per NCCN guidelines is allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (See Appendix A)
• Life expectancy of greater than 12 weeks.
• Ability to take oral medications.
• Informed consent: participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• Participants with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiation, or stereotactic radiosurgery) for at least 1 month.
• Participants must have adequate normal organ and bone marrow function as defined below:
‣ Absolute neutrophil count \>/= 1,000/mcL
⁃ Hemoglobin \>/= 9.0 g/dL
⁃ Platelets \>/= 100,000/mcL
⁃ Total bilirubin \</= 1.5 x upper limit of normal (ULN)
⁃ AST (SGOT)/ ALT (SGPT) \</= 2.5 x ULN; \</= 5 x ULN in the setting of metastatic liver disease
⁃ Creatinine \</= 1.5 x ULN or creatinine clearance \>/= 50 mL/min