An interventional study of FoundationOne® Liquid CDx (F1LCDx) and Reflex tissue biopsy in Breast Cancer, Metastatic Breast Cancer and HR+/HER- Metastatic Breast Cancer, sponsored by Yale University. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by Yale University · Not applicable, Interventional, and Diagnostic
This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer.
Participants are prospectively assigned to undergo ctDNA testing with FoundationOne® Liquid CDx (F1LCDx) at protocol-defined clinical decision points. Participants with an indeterminate negative F1LCDx result (ctDNA TF \<1% and negative for ESR1mut) are assigned to undergo reflex tissue biopsy NGS unless deemed medically unsafe. The protocol does not mandate treatment selection; treating clinicians retain full discretion regarding therapy.All research-related procedures will be performed at the time of standard of care clinical visits. No extra visits outside of routine care are required. For participants with algorithm-detected ESR1 mutations, serial Electronic Medical Record review will be performed for up to 2 years to track subsequent treatment patterns, progression events, and survival status to assess other clinical outcomes associated with subsequent SERD-based regimens compared with historical clinical trial benchmarks.
This study will guide clinical decision-making for acquiring new tissue specimens following an indeterminate negative ESR1mut result from liquid biopsy, which is a critical step to ensure accurate detection of actionable mutations and enable the selection of the most appropriate targeted therapy
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's planned enrollment of 155 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Yale University is the lead sponsor of 1,770 studies on the registry; 294 are open to participants now.
Of its 221 completed or terminated interventional studies of FDA-regulated products, 129 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Nov 5, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with ESR1 mutations in HR+/HER- metastatic breast cancer undergoing tissue biopsy for ctDNA Tumor Fraction (TF) testing using next-generation sequencing (NGS) after an indeterminate negative result in liquid biopsy (F1LCDx).
Diagnostic Test: FoundationOne® Liquid CDx (F1LCDx) · Diagnostic Test: Reflex tissue biopsy
Blood test that analyzes cancer-related genes from a single blood draw
Reflex tissue biopsy using an Next-generation sequencing (NGS) test
Number of participants with ESR1 mutations detected by reflex tissue NGS
Among participants with an indeterminate-negative liquid biopsy result (negative for ESR1 mutations and ctDNA tumor fraction below 1%), measure the number of participants with an ESR1 mutation detected by reflex tissue NGS performed according to the study algorithm.
Time frame: From enrollment through study completion (up to 5 years)
Progression-free survival (PFS)
Time from initiation of the first selective estrogen receptor degrader (SERD) after ESR1 mutation detection until objective disease progression, assessed using RECIST version 1.1 when available, or death from any cause, whichever occurs first.
Time frame: Up to 2 years after positive ESR1 mutation detection
Rate of ESR1 mutation detection by liquid biopsy and ctDNA tumor fraction
Rate of ESR1 mutation detection by FoundationOne Liquid CDx (F1LCDx), stratified by ctDNA tumor fraction below 1% versus 1% or greater.
Time frame: Throughout the study, up to 5 years
Reflex Tissue NGS testing rate
Number of participants with an indeterminate-negative liquid biopsy result who undergo reflex tissue biopsy and NGS within the protocol-defined timeframe.
Time frame: Within the reflex testing time frame during the study, up to 5 years
Number participants initiating Selective Estrogen Receptor Degraders (SERD) therapy
Number participants initiating SERD therapy after ESR1 mutation detection
Time frame: Throughout the study, up to 5 years
Number participants SERD therapy by SERD agent
Number participants initiating SERD therapy after ESR1 mutation detection. Report counts by SERD agent, with FDA-approved SERDs grouped by class as applicable.
Time frame: Throughout the study, up to 5 years
Actionable genomic alterations detected by liquid biopsy and tissue NGS.
Rtes of actionable genomic alterations detected by F1LCDx and tissue NGS.
Time frame: Throughout the study, up to 5 years
Other genomic alterations detected at disease progression
Rates of driver and acquired genomic alterations detected at progression by F1LCDx or tissue NGS that were absent from prior tissue comprehensive genomic profiling (CGP). Acquired alterations are those absent from tissue CGP at diagnosis but newly detected at progression.
Time frame: At disease progression during the study, up to 5 years
Correlation of HRR gene findings with variant origin and germline confirmation
Assess the relationship between homologous recombination repair (HRR) gene detection, variant origin prediction, germline banner classification when F1LCDx is performed, and confirmation of germline alterations by orthogonal testing.
Time frame: During the study, when the relevant genomic and confirmatory testing results are available, up to 5 years
Correlation of HER2 status with ERBB2 copy number
Assess the relationship between HER2-low or HER2-negative status and ERBB2 copy number results when F1CDx is performed.
Time frame: During the study, when the relevant HER2 status and genomic results are available, up to 5 years
Plan to share: No
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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