SHIELD: Surveillance of HR+/HER2- : Implementing ESR1m Long-term Monitoring and Detection in 1L aBC

NCT07701070 | Not Yet Recruiting

• 1 other identifier: D9673L00023
• Study Type: observational
• Target: 3,000
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Prevalence of ESR1 mutations in circulating tumour DNA

  Number and proportion of patients with at least one ESR1 mutation

  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

  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

  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

  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

  At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing

• Distribution of ESR1 mutation subtypes and allele frequency

  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

  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

  At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing

Study Arms (1)

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.

Other: Blood sampling

Interventions

Blood sampling OTHER

Blood sampling for ctDNA-based ESR1 mutation testing, which are associated with minimal additional risk and burden compared with routine clinical practice

Participants with HR-positive, HER2-negative advanced breast cancer

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Food and Drug Administration (FDA): collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Blood sampling

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

+1877240-9479; information.center@astrazeneca.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 30, 2029
• Last Updated: July 14, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.