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

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.

• 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]