A Study of JNJ-101684362 (HLD-0117) in Patients With Metastatic Breast Cancer

Female (assigned at birth), greater than or equal to (>=) 18 years old, and able to provide informed consent

Histologically confirmed metastatic or locally advanced breast cancer

Postmenopausal status defined by surgical or natural menopause, or ovarian suppression with a GnRH agonist

Prior therapy including

1. Must have received at least one endocrine therapy in the metastatic setting.
2. Must have received at least one cyclin-dependent kinase (CDK) 4/6i, either in the adjuvant and/or metastatic setting.
3. For Part 1 and Part 2 Cohorts 2A, 2B, 2C, and 2D: Participants may have received up to two prior distinct cytotoxic regimens (for example, taxanes, antibody-drug conjugates (ADCs), etc.) in the metastatic setting, unless discussed and approved by the medical monitor.
4. For Part 2 Cohort 2E: Participants must have received more than two prior distinct cytotoxic regimens (for example, taxanes, ADCs, etc.) in the metastatic setting.

Radiologic disease progression on the most recent therapy

Patients must have disease evaluable per response evaluation criteria in solid tumors (RECIST) v1.1

1. For Part 1 and Part 2B, 2C, and 2E: Participants may have either evaluable or measurable disease per RECIST v1.1.
2. For Part 2 Cohort 2A: Participants should have measurable soft tissue disease per RECIST v1.1.
3. For Part 2 Cohort 2D: Participants should have evaluable but not measurable disease.

Willingness to provide baseline and on-treatment tumor biopsies, unless not feasible or medically appropriate

For Part 1 and Part 2 (all cohorts):

1. Participants must have documented >=10% ER staining and human epidermal growth factor receptor 2 (HER2) negative (per american society of clinical oncology [ASCO] college of american pathologists [CAP] guidelines) on the most recent tumor biopsy sample obtained.
2. For Part 2 Cohort 2B: Participants must have recent estrogen receptor 1 gene (ESR1) wild type from tumor or circulating tumor deoxy ribonucleic acid (ctDNA) testing performed after the most recent endocrine therapy prior to enrollment.
3. For Part 2 Cohort 2C: Participants must have ESR1 mutation detected from tumor or ctDNA testing performed prior to enrollment.

Eastern cooperative oncology group (ECOG) performance status 0-1 and life expectancy of at least 3 months

Adequate organ function Recovery from prior therapy-related toxicities to Grade <=1 (except alopecia; neuropathy and endocrinopathies <=Grade 2)

Ability to swallow oral medication and comply with study procedures

Stable dose (>=30 days) of bisphosphonates or denosumab, if applicable