A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Eligibility Criteria

• * Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
• * Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
• * Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
• * Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after \>/=12 months or off-treatment within 12 months of completion. Prior use of neo/adjuvant CDK4/6i is allowed.
• * No prior systemic anti-cancer therapy for advanced disease
• * Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
• * Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
• * For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment
• * Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
• * Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
• * Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
• * Active cardiac disease or history of cardiac dysfunction
• * Clinically significant history of liver disease