This study is about finding the best **second-line treatment** for patients with a certain type of breast cancer. The study uses a test called **Signatera** to check for **circulating tumor DNA (ctDNA)**, which can help detect cancer returning.

The study is for patients with **high-risk, ER-positive, HER2-negative breast cancer** who have finished or are still on a specific cancer treatment called **adjuvant endocrine therapy**, like tamoxifen or aromatase inhibitors. Patients must have completed at least 6 months to 7 years of this treatment to join. They need to have their breast cancer tissue available for testing and sign a consent form.

If a patient's test shows positive ctDNA, they will have a CT scan and may join a treatment plan involving medicines like **palbociclib** and **fulvestrant** for up to 2 years.

• The maximum length of the study treatment is 2 years.
• Patients may need to visit the clinic every 4 to 6 months.
• Participants should discuss potential risks and side effects with their doctor.