Advanced Breast CancerSHIELDNCT07701070
SHIELD: Surveillance of HR+/HER2- : Implementing ESR1m Long-term Monitoring and Detection in 1L aBC
An observational study of Advanced Breast Cancer, run by AstraZeneca.
Trial summary
This is a multicountry, multicenter, observational study in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer receiving first-line endocrine-based therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Blood sampling
- How many people
- 3,000 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2026to 30 Mar 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with HR-positive/HER2-negative advanced breast cancer (aBC), receiving first-line aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy for 6-18 months, without disease progression, and with unknown ESR1 status at baseline.
Who may be able to join
- Age 18 years or older at the time of informed consent and willing and able to provide informed consent before any study-related procedures.
- Histologically- or cytologically-confirmed hormone receptor-positive (ER- and/or progesterone receptor-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer.
- Receiving first-line therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor for at least 6 months and no more than 18 months, with no evidence of disease progression at study entry, as assessed by the investigator.
- Able and willing to provide a blood sample for circulating tumour DNA testing for ESR1 mutation assessment at approximately quarterly intervals.
Who cannot join
- Evidence of disease progression during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy, based on investigator assessment.
- Known ESR1 mutation status at study entry.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
About this study
Official title: A Multicenter Study to Describe the Frequency and Emergence of ESR1 Mutations in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving First-Line Endocrine Based Therapy
This is a multicountry, multicenter, observational study in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer receiving first-line endocrine-based therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor. The study aims to describe the prevalence of ESR1 mutations at baseline and the emergence of ESR1 mutations over time using circulating tumor DNA testing in routine clinical practice.
Patients receiving first-line treatment for at least 6 months and no more than 18 months, without evidence of disease progression at study entry, may undergo baseline ESR1 mutation testing. Patients with a negative baseline result may undergo longitudinal monitoring approximately every 3 months, for up to 18 months or 6 testing timepoints, to assess emergence of ESR1 mutations. The study will also describe mutation subtypes, testing methods used in routine practice, selected clinical characteristics, and treatment patterns across participating countries.
Read the detailed description
This is a multicountry, multicenter, observational study designed to determine the prevalence of ESR1 mutations at baseline and to assess the emergence of ESR1 mutations during longitudinal surveillance in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) receiving first-line treatment with an aromatase inhibitor (AI) in combination with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Eligible patients are adults with histologically or cytologically confirmed HR+/HER2- advanced breast cancer who have been receiving first-line AI plus CDK4/6 inhibitor therapy for at least 6 months and no more than 18 months, without evidence of disease progression according to investigator assessment, and who are willing and able to provide blood samples for circulating tumor DNA (ctDNA) testing at predefined intervals.
Following informed consent, baseline data will be collected in electronic case report forms and will include sociodemographic characteristics, clinical and tumor history, testing methods, and treatment patterns. A baseline blood sample will be collected for ctDNA-based ESR1 mutation testing using testing methods applied in routine clinical practice, including but not limited to quantitative polymerase chain reaction (qPCR), digital polymerase chain reaction (dPCR), and next-generation sequencing (NGS), according to local availability and site capability. Testing will be performed in validated laboratories in accordance with local standard operating procedures.
Patients who are negative for ESR1 mutation at baseline will undergo longitudinal ctDNA monitoring approximately every 12 weeks (+/-4 weeks), for up to 18 months or 6 testing time points from initial testing, whichever occurs first. Patients who test positive for ESR1 mutation at baseline or during follow-up will discontinue further study surveillance and will continue to receive routine clinical care as determined by the treating physician. The date of first ESR1 mutation detection will be recorded.
The primary objectives are to determine the prevalence of ESR1 mutations at baseline and the emergence rate and time to emergence of ESR1 mutations during the surveillance period among patients who are ESR1 negative at initial testing. Secondary objectives include assessment of ESR1 mutation frequency by duration of first-line therapy and by testing method, distribution of specific ESR1 mutation subtypes, co-mutations with other clinically relevant biomarkers when available, patient clinical and sociodemographic characteristics, testing and treatment patterns, and associations between ESR1 mutation status and relevant patient or treatment factors.
Approximately 3,000 patients are planned to be enrolled at about 30 sites in 15 countries across Asia, Latin America, and the Middle East and Africa. The estimated recruitment period is 12 months.
- Conditions
- Advanced Breast Cancer
- Being tested
- Blood sampling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingOther
Blood sampling for ctDNA-based ESR1 mutation testing, which are associated with minimal additional risk and burden compared with routine clinical practice
| Study group | Role | What they receive |
|---|---|---|
| Participants with HR-positive, HER2-negative advanced breast cancer | Adults with HR-positive, HER2-negative advanced breast cancer receiving first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor for 6 to 18 months without disease progression at study entry. Participants undergo baseline ESR1 mutation testing using circulating tumour DNA; those with a negative baseline result may undergo follow-up testing approximately every 3 months for up to 18 months. Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of ESR1 mutations in circulating tumour DNA
Number and proportion of patients with at least one ESR1 mutation
Measured: At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Emergence of ESR1 mutations during longitudinal ctDNA surveillance
Number and proportion of patients who are detected with ESR1 mutation
Measured: At approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Time to first detection of an ESR1 mutation
Time in months from initiation of first-line treatment with AI and CDK4/6 inhibitors to first detection of ESR1mutation
Measured: From first-line AI plus CDK4/6 inhibitor initiation to first ESR1 mutation detection
Secondary outcomes (8)
Prevalence of ESR1 mutations by duration of ongoing first-line AI plus CDK4/6 inhibitor therapy
Number and proportion of participants with ESR1 mutations by duration of ongoing first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor
Measured: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Frequency of ESR1 mutation-positive results by testing method
Number and proportion of participants with ESR1 mutation-positive results according to the circulating tumour DNA testing method used.
Measured: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Distribution of ESR1 mutation subtypes and allele frequency
Number and proportion of participants with specific ESR1 mutation subtypes detected by circulating tumour DNA testing.
Measured: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Frequency of additional co-mutations among ESR1 mutation-positive participants
Number and proportion of participants with ESR1 mutations who have at least 1 additional clinically relevant co-mutation detected, where available.
Measured: At baseline and approximately every 3 months through study completion, up to approximately 18 months after initial ESR1 testing
Baseline and follow-up characteristics of the study population
Summary of selected sociodemographic, clinical, tumour, and testing characteristics of the study population.
Measured: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Relationship between ESR1 mutation status and selected participant and treatment characteristics
Assessment of the relationship between ESR1 mutation status and selected participant, disease, testing, and treatment characteristics.
Measured: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Treatment patterns for advanced breast cancer
Summary of first-line treatment regimens for advanced breast cancer, including endocrine therapy and CDK4/6 inhibitor use, and duration of therapy.
Measured: From enrolment through study completion, up to approximately 18 months after initial ESR1 testing
Prior treatment patterns for early-stage breast cancer
Summary of prior therapies received for early-stage breast cancer in participants who later developed advanced breast cancer, including duration of therapy and reasons for discontinuation, where available.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2026
- Study start30 Sep 2026 (estimated)
- Primary completion30 Mar 2029 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07701070
- Sponsor's protocol ID
- D9673L00023
- Acronym
- SHIELD
- Status last verified
- Jun 2026
- First submitted
- 8 Jul 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Study to Describe the Frequency and Emergence of ESR1 Mutations in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving First-Line Endocrine Based Therapy
- ClinicalTrials.gov ID
- NCT07701070
- Acronym / sponsor ID
- SHIELD / D9673L00023
- Conditions
- Advanced Breast Cancer
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 30 Sep 2026 (estimated)
- Primary completion
- 30 Mar 2029 (estimated)
- Study completion
- 30 Mar 2029 (estimated)
- First posted
- 14 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicountry, multicenter, observational study in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer receiving first-line endocrine-based therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor. The study aims to describe the prevalence of ESR1 mutations at baseline and the emergence of ESR1 mutations over time using circulating tumor DNA testing in routine clinical practice.
Patients receiving first-line treatment for at least 6 months and no more than 18 months, without evidence of disease progression at study entry, may undergo baseline ESR1 mutation testing. Patients with a negative baseline result may undergo longitudinal monitoring approximately every 3 months, for up to 18 months or 6 testing timepoints, to assess emergence of ESR1 mutations. The study will also describe mutation subtypes, testing methods used in routine practice, selected clinical characteristics, and treatment patterns across participating countries.
Detailed description
This is a multicountry, multicenter, observational study designed to determine the prevalence of ESR1 mutations at baseline and to assess the emergence of ESR1 mutations during longitudinal surveillance in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) receiving first-line treatment with an aromatase inhibitor (AI) in combination with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Eligible patients are adults with histologically or cytologically confirmed HR+/HER2- advanced breast cancer who have been receiving first-line AI plus CDK4/6 inhibitor therapy for at least 6 months and no more than 18 months, without evidence of disease progression according to investigator assessment, and who are willing and able to provide blood samples for circulating tumor DNA (ctDNA) testing at predefined intervals.
Following informed consent, baseline data will be collected in electronic case report forms and will include sociodemographic characteristics, clinical and tumor history, testing methods, and treatment patterns. A baseline blood sample will be collected for ctDNA-based ESR1 mutation testing using testing methods applied in routine clinical practice, including but not limited to quantitative polymerase chain reaction (qPCR), digital polymerase chain reaction (dPCR), and next-generation sequencing (NGS), according to local availability and site capability. Testing will be performed in validated laboratories in accordance with local standard operating procedures.
Patients who are negative for ESR1 mutation at baseline will undergo longitudinal ctDNA monitoring approximately every 12 weeks (+/-4 weeks), for up to 18 months or 6 testing time points from initial testing, whichever occurs first. Patients who test positive for ESR1 mutation at baseline or during follow-up will discontinue further study surveillance and will continue to receive routine clinical care as determined by the treating physician. The date of first ESR1 mutation detection will be recorded.
The primary objectives are to determine the prevalence of ESR1 mutations at baseline and the emergence rate and time to emergence of ESR1 mutations during the surveillance period among patients who are ESR1 negative at initial testing. Secondary objectives include assessment of ESR1 mutation frequency by duration of first-line therapy and by testing method, distribution of specific ESR1 mutation subtypes, co-mutations with other clinically relevant biomarkers when available, patient clinical and sociodemographic characteristics, testing and treatment patterns, and associations between ESR1 mutation status and relevant patient or treatment factors.
Approximately 3,000 patients are planned to be enrolled at about 30 sites in 15 countries across Asia, Latin America, and the Middle East and Africa. The estimated recruitment period is 12 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with HR-positive, HER2-negative advanced breast cancer | – | Other: Blood samplingAdults with HR-positive, HER2-negative advanced breast cancer receiving first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor for 6 to 18 months without disease progression at study entry. Participants undergo baseline ESR1 mutation testing using circulating tumour DNA; those with a negative baseline result may undergo follow-up testing approximately every 3 months for up to 18 months. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with HR-positive/HER2-negative advanced breast cancer (aBC), receiving first-line aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy for 6-18 months, without disease progression, and with unknown ESR1 status at baseline.
Key inclusion criteria (4 listed)
- Age 18 years or older at the time of informed consent and willing and able to provide informed consent before any study-related procedures.
- Histologically- or cytologically-confirmed hormone receptor-positive (ER- and/or progesterone receptor-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer.
- Receiving first-line therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor for at least 6 months and no more than 18 months, with no evidence of disease progression at study entry, as assessed by the investigator.
- Able and willing to provide a blood sample for circulating tumour DNA testing for ESR1 mutation assessment at approximately quarterly intervals.
Key exclusion criteria (2 listed)
- Evidence of disease progression during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy, based on investigator assessment.
- Known ESR1 mutation status at study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplingBlood sampling for ctDNA-based ESR1 mutation testing, which are associated with minimal additional risk and burden compared with routine clinical practice | Other | Participants with HR-positive, HER2-negative advanced breast cancer |
Primary outcome
Prevalence of ESR1 mutations in circulating tumour DNA
Time frame: At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Number and proportion of patients with at least one ESR1 mutation
Emergence of ESR1 mutations during longitudinal ctDNA surveillance
Time frame: At approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Number and proportion of patients who are detected with ESR1 mutation
Time to first detection of an ESR1 mutation
Time frame: From first-line AI plus CDK4/6 inhibitor initiation to first ESR1 mutation detection
Time in months from initiation of first-line treatment with AI and CDK4/6 inhibitors to first detection of ESR1mutation
8 secondary outcomes
Prevalence of ESR1 mutations by duration of ongoing first-line AI plus CDK4/6 inhibitor therapy
Time frame: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Frequency of ESR1 mutation-positive results by testing method
Time frame: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Distribution of ESR1 mutation subtypes and allele frequency
Time frame: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Frequency of additional co-mutations among ESR1 mutation-positive participants
Time frame: At baseline and approximately every 3 months through study completion, up to approximately 18 months after initial ESR1 testing
Baseline and follow-up characteristics of the study population
Time frame: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Relationship between ESR1 mutation status and selected participant and treatment characteristics
Time frame: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
Treatment patterns for advanced breast cancer
Time frame: From enrolment through study completion, up to approximately 18 months after initial ESR1 testing
Prior treatment patterns for early-stage breast cancer
Time frame: At baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
Questions about this trial
What is this clinical trial studying?
An observational study of Advanced Breast Cancer, run by AstraZeneca.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (+1877240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of ESR1 mutations in circulating tumour DNA (time frame: At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.