An interventional study of ESR1 testing in HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole), sponsored by Institut fuer Frauengesundheit. Not yet recruiting at 21 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by Institut fuer Frauengesundheit · Not applicable, Interventional, and Diagnostic
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Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. This combination therapy is usually given until clinical progression.
Recent studies suggest that a detection of a somatic ESR1 mutation in the ctDNA can be clinically used to prompt an earlier change from the aromatase inhibitor to a selective estrogen receptor degrader.
For implementation in the clinical routine it is important to gain knowledge about the dynamics of ESR1 mutation in HR+/HER2- advanced breast cancer patients during their first line therapy. At the beginning of the first line therapy about 5-8% of patients show an ESR1 mutation. An identification of patients with resistance to aromatase inhibitors at that timepoint might not be feasible and cost-efficient. At the timepoint of clinical progression up to 30-40% of patients will have acquired an ESR1 mutation. Knowledge about the mutation frequencies at different timepoints will be very helpful to direct testing strategies for implementing testing broadly in a population.
The aim of this study is to test ESR1 mutation frequencies in groups of patients (single time test per patient) with no clinical progression and different durations under first-line treatment with aromatase inhibitor and CDK4/4 inhibitor.
Institut fuer Frauengesundheit is the lead sponsor of 12 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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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.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before start of the 1L treatment (anticipated AI + CDK4/6i)
Diagnostic Test: ESR1 testing
Patients in months 6, 7 or 8 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 9, 10 or 11 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 12, 13 or 14 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 15, 16 or 17 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 18, 19 or 20 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 21, 22 or 23 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 24, 25 or 26 of the 1L treatment
Diagnostic Test: ESR1 testing
Patients in months 27, 28 or 29 of the 1L treatment
Diagnostic Test: ESR1 testing
Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
PO1
mutation frequency of ESR1 mutations as assessed in blood sample
Time frame: Day 1
SO1
ESR1 mutation frequencies according to age and BMI
Time frame: Day 1
SO2
ESR1 mutation frequencies according to type of CDK4/6i therapy
Time frame: Day 1
SO3
ESR1 mutation frequencies according to type of aromatase inhibitor
Time frame: Day 1
SO3
ESR1 mutation frequencies according to menopausal status
Time frame: Day 1
SO4
ESR1 mutation frequencies according to HER2 status (HER2 0, HER2 ultralow, HER2 low)
Time frame: Day 1
SO5
ESR1 mutation frequencies according to extent of estrogen and progesterone receptor expression
Time frame: Day 1
SO6
ESR1 mutation frequencies according to tumor grading
Time frame: Day 1
SO7
ESR1 mutation frequencies according to previous therapies (de novo patients vs. previous adjuvant therapy)
Time frame: Day 1
EO1
To explore the molecular landscape accompanying ESR1 mutations, including co-occurring genomic alterations (e.g., PIK3CA, TP53, etc.) detected in ctDNA
Time frame: Day 1
EO2
To investigate associations between ESR1 mutation characteristics (variant type, allele frequency) and clinical or molecular features, including prior AI exposure.
Time frame: Day 1
EO3
To perform transcriptomic profiling (bulk RNA-seq) of circulating immune cells (PBMCs) to identify immune activation or suppression signatures associated with clinical progression (PD vs. non-PD).
Time frame: Day 1
EO4
To explore potential biomarkers of endocrine resistance and immune modulation, integrating ctDNA muta
Time frame: Day 1
Plan to share: Undecided
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Oct 2027, 12 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Institut fuer Frauengesundheit