Predicting Endocrine Resistance Using Molecular Imaging and Liquid Biopsy in Metastatic Breast Cancer

NCT07867925 | Not Yet Recruiting

• 1 other identifier: PREDICT-ER
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study aims to evaluate the prognostic value of molecular imaging biomarkers derived from baseline \[18F\]FES and \[18F\]FDG PET/CT for progression-free survival in patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer receiving first-line endocrine therapy combined with a CDK4/6 inhibitor. In a subset of patients with available tumor tissue, paired tumor tissue next-generation sequencing (NGS) and circulating tumor DNA (ctDNA) analysis will also be performed to investigate their associations with imaging biomarkers, treatment response, and clinical outcomes.

Conditions

Metastatic Breast Cancer (HR+/ HER2-)

Keywords

breast cancer; [18F]FES PET/CT; [18F]FDG PET/CT; Endocrine therapy; Endocrine resistance; ctDNA

Outcome Measures

Primary Outcomes (1)

• Prognostic value of baseline [18F]FES and [18F]FDG PET/CT-derived molecular imaging biomarkers for progression-free survival

  Association of baseline molecular imaging biomarkers derived from \[18F\]FES and \[18F\]FDG PET/CT with progression-free survival (PFS) during first-line endocrine therapy combined with a CDK4/6 inhibitor

  From initiation of first-line endocrine therapy until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months.

Secondary Outcomes (4)

• Prognostic value of baseline ctDNA-based liquid biopsy biomarkers for progression-free survival

  From initiation of first-line endocrine therapy until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months.

• Prognostic value of baseline tumor tissue NGS findings for progression-free survival

  From initiation of first-line endocrine therapy until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months.

• Prognostic value of changes in ctDNA-based liquid biopsy biomarkers at 12 weeks for progression-free survival

  From 12 weeks after treatment initiation until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months after treatment initiation.

• Association among baseline molecular imaging biomarkers, ctDNA-based liquid biopsy biomarkers, and tumor tissue NGS findings

  At baseline, before initiation of first-line endocrine therapy.

Other Outcomes (5)

• Prognostic value of changes in [18F]FDG PET/CT at 12 weeks for progression-free survival

  From 12 weeks after treatment initiation until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months after treatment initiation.

• Association between changes in [18F]FDG PET/CT and changes in ctDNA-based liquid biopsy biomarkers at 12 weeks

  From baseline to approximately 12 weeks after treatment initiation.

• Association among molecular imaging biomarkers, ctDNA-based liquid biopsy biomarkers, and tumor tissue NGS findings at disease progression

  At the time of first documented disease progression, assessed up to 48 months after initiation of first-line endocrine therapy.

Study Arms (1)

ER-Positive, HER2-Negative Metastatic Breast Cancer

Participants with ER-positive, HER2-negative metastatic breast cancer who are scheduled to receive first-line endocrine therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor.

Diagnostic Test: [18F] FES

Interventions

[18F] FES DIAGNOSTIC_TEST

Participants will undergo baseline 18F-fluoroestradiol (\[18F\]FES) PET/CT before initiation of first-line endocrine therapy combined with a CDK4/6 inhibitor. \[18F\]FES (111-222 MBq) will be administered intravenously, and whole-body PET/CT imaging will be performed according to the institutional imaging protocol. \[18F\]FES PET/CT will be used to assess estrogen receptor expression and heterogeneity across metastatic lesions.

ER-Positive, HER2-Negative Metastatic Breast Cancer

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with ER-positive, HER2-negative metastatic breast cancer who are scheduled to initiate first-line endocrine therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor at Asan Medical Center. Potentially eligible patients will be identified from the medical oncology outpatient clinic or inpatient wards and prospectively enrolled according to the predefined eligibility criteria.

You may qualify if:

• Male or female participants aged 19 years or older, regardless of race or ethnicity.
• Histologically confirmed invasive breast cancer that is ER-positive and HER2-negative by immunohistochemistry.
• Scheduled to initiate first-line systemic endocrine therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor for metastatic breast cancer within 60 days of screening.
• Have undergone or be scheduled to undergo \[18F\]FDG PET/CT before initiation of endocrine therapy combined with a CDK4/6 inhibitor.
• Have measurable or clinically evaluable metastatic disease on standard-of-care imaging.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

You may not qualify if:

• Failure of the participant or the participant's legally authorized representative to provide written informed consent.
• History of another invasive malignancy within the previous 2 years, except for non-melanoma skin cancer.
• Absence of lesions with significant uptake on \[18F\]FDG PET/CT, or inability to quantitatively evaluate major lesions because of lesion location (e.g., brain or other sites with high physiologic uptake), severe motion artifacts, reconstruction errors, or other technical limitations.
• Metastatic disease confined exclusively to the liver on imaging.
• Previous systemic treatment for metastatic breast cancer, including endocrine therapy, targeted therapy, or anticancer chemotherapy including antibody-drug conjugates (ADCs).
• Pregnancy or breastfeeding. Participants are considered not to be of childbearing potential if they are physiologically postmenopausal (amenorrhea for at least 2 years) or surgically sterile (documented bilateral oophorectomy or hysterectomy). Participants of childbearing potential must have a negative serum or urine pregnancy test within 24 hours before \[18F\]FES administration and must use contraception during the study period.
• Serious, uncontrolled, and/or unstable medical conditions, including but not limited to congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic kidney disease, or chronic liver disease.
• Being a relative or student of an investigator or otherwise having a dependent relationship with an investigator.
• Any personal circumstances or other conditions that, in the investigator's judgment, are likely to prevent complete collection of study data.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sangwon Han, Clinical assistant professor

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sangwon Han

CONTACT

+82-2-3010-0657; hswon87@amc.seoul.kr

Jaeeun Kim

CONTACT

+82-2-3010-4572; kje0216@amc.seoul.kr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical assistant professor

Study Record Dates

• First Submitted: August 19, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): October 13, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)