Inclusion Criteria:

          -  Participant has signed informed consent form (ICF) before any trial related activities
             and according to local guidelines.

          -  Only females are eligible. Menopausal status:

             i. Postmenopausal defined by:

               1. Prior bilateral oophorectomy;

               2. Age ≥60 years; or

               3. Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy,
                  tamoxifen, toremifen, or ovarian suppression) and follicle-stimulating hormone
                  (FSH) value >40 milli-international units per milliliter (mIU/mL) and an
                  estradiol value <40 picograms per milliliter (pg/mL) (140 picomoles per liter
                  [pmol/L]).

                  Or ii. Premenopausal or perimenopausal concurrently given a luteinizing
                  hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the
                  start of trial therapy and is planned to continue LHRH during the study.

          -  Participant has a histologically and/or cytologically confirmed diagnosis of
             estrogen-receptor (ER) positive breast cancer by local laboratory.

          -  Participant has human epidermal growth factor receptor 2 (HER2) negative breast cancer
             as defined by American Society of Clinical Oncology (ASCO)-College of American
             Pathologists guidelines.

          -  Participant must have progressed on the most recent therapy.

          -  Prior therapy for breast cancer in the advanced/metastatic setting must have included
             at least:

               1. two prior hormonal therapies;

               2. one prior hormonal therapy and one prior chemotherapy regimen; or

               3. one prior hormonal therapy and a Cyclin-dependent kinase (CDK)4/6 inhibitor.
                  Note: Participants may have received treatment for brain metastases, but must be
                  neurologically stable, completed radiotherapy and off corticosteroids for at
                  least one month prior to starting trial therapy.

          -  Participant must have at least one biopsiable lesion in the Phase 1 portion. In the
             Phase 2 part of the trial, participants must have either (a) at least one measurable
             lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or (b) at
             least one predominantly lytic bone lesion.

          -  Participant must be willing to undergo tumor biopsies prior to treatment and on Cycle
             2 Day 1. In the Phase 2 part of the trial, participants with bone-only disease, or
             participants for whom a biopsy is contra-indicated, may opt out of providing tumor
             biopsies. Note: A subset of participants in Phase 2 will be required to provide tumor
             tissue until tumor pairs have been collected from at least 15 ER˄WT and 15 ER˄mut
             (determined by sponsor-designated central laboratory test).

          -  Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS)
             of 0 or 1.

          -  Participant has adequate bone marrow and organ function as defined by the following
             laboratory values:

               1. Absolute neutrophil count (ANC) ≥1.5 × 10˄9/Liter (L);

               2. Platelets ≥100 × 10˄9/L;

               3. Hemoglobin ≥9.0 grams per deciliter (g/dL);

               4. Potassium, sodium, calcium (corrected for serum albumin), magnesium, and
                  phosphorus within normal limits for the institution;

               5. International normalized ratio (INR) ≤1.5;

               6. Serum creatinine ≤1.5 × upper limit of normal (ULN);

               7. Serum albumin ≥3.5 g/dL (≥35 grams per liter (g/L));

               8. In the absence of liver metastases, alanine aminotransferase (AST) and aspartate
                  aminotransferase (ALT) should be below 3.0 × ULN. If the participant has liver
                  metastases, ALT and AST should be below 5.0 × ULN.

               9. Total serum bilirubin less than ULN.

          -  Willingness and ability to comply with study and follow-up procedures.

          -  Ability to understand the nature of this study and give written informed consent.

        Exclusion Criteria:

          -  Participant with bone-only disease (Phase 1 only). Note: Phase 2 participants may have
             predominantly lytic bone-only disease.

          -  Participant with inflammatory breast cancer.

          -  Participant has received more than one prior chemotherapy regimen for metastatic
             disease.

          -  Participant has had prior antineoplastic therapy within 14 days prior to starting
             study drug.

          -  Participant is currently receiving or has received systemic corticosteroids ≤2 weeks
             prior to starting study drug, or has not fully recovered from side effects of such
             treatment.

        Note: The following uses of corticosteroids are permitted: single doses, topical
        applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye
        drops, or local injections (e.g., intra-articular).

          -  Participant has received radiotherapy ≤4 weeks or limited field radiation for
             palliation ≤2 weeks prior to starting study drug, and who has not recovered to Grade 1
             or better from related side effects of such therapy (with the exception of alopecia)
             and/or for whom ≥30% of the bone marrow was irradiated.

          -  Major surgical procedures ≤14 days of beginning study drug, or minor surgical
             procedures ≤7 days, or has not recovered from major side effects. No waiting required
             following port-a-cath placement.

          -  Participant has active cardiac disease or a history of cardiac dysfunction including
             any of the following:

               1. History of angina pectoris, symptomatic pericarditis, or myocardial infarction
                  within 12 months prior to study entry;

               2. History of documented congestive heart failure (New York Heart Association
                  functional classification III-IV);

               3. Documented cardiomyopathy;

               4. Participant has a left ventricular ejection fraction (LVEF) <50% as determined by
                  multiple gated acquisition (MUGA) scan or echocardiogram (ECHO);

               5. History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal
                  arrhythmias, or conduction abnormality in the previous 12 months;

               6. On screening, any of the following cardiac parameters: interval between P and R
                  (PR interval) >220 milliseconds (msec), interval between Q, R, and S (QRS)
                  interval >109 msec, or QT interval corrected for heart rate using Fridericia's
                  formula (QTcF) >450 msec;

               7. Systolic blood pressure (BP) not deemed clinically controlled by the
                  investigator.

          -  Participant has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of H3B-6545 (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection).

          -  Participant has a known hypersensitivity to any of the excipients of H3B-6545.

          -  Participant has a known history of human immunodeficiency virus (HIV) infection or
             hepatitis C virus (HCV), or requires treatment with protease inhibitors (testing not
             mandatory).

          -  Participant has any other concurrent severe and/or uncontrolled medical condition that
             would, in the investigator's judgment, contraindicate participant participation in the
             clinical study (e.g., chronic pancreatitis, active hepatitis, etc.).

          -  Participant that received in the 7 days prior to the administration of study drug or
             is currently receiving any of the following medications:

               1. Known strong inducers or inhibitors of cytochrome (CYP)3A4 or P-glycoprotein
                  (P-gp);

               2. Medications that have a known risk to prolong the QT interval or induce Torsades
                  de Pointes;

               3. Proton-pump inhibitors and histamine H2-receptor antagonists;

               4. Medications that have a narrow therapeutic window and are predominantly
                  metabolized through CYP2C8, CYP2C9, CYP2C19, or CYP3A4;

               5. Herbal preparations/medications. These herbal medications include, but are not
                  limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba,
                  dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.

          -  Any adverse events related to previous therapies for breast cancer that have not
             resolved to ≤Grade 1.

          -  Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin
             [hCG]) test with a minimum sensitivity of 25 International units per liter [IU/L] or
             equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a
             negative screening pregnancy test was obtained more than 72 hours before the first
             dose of study drug.

          -  Females of childbearing potential who:

               1. Had unprotected sexual intercourse within 30 days before study entry and who do
                  not agree to use a highly effective method of contraception (e.g., total
                  abstinence, an intrauterine device, a double-barrier method [such as condom plus
                  diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or
                  have a vasectomized partner with confirmed azoospermia) throughout the entire
                  study period or for 28 days after study drug discontinuation.

               2. Are currently abstinent, and do not agree to use a double-barrier method (as
                  described above) or refrain from sexual activity during the study period or for
                  28 days after study drug discontinuation.

               3. Are using hormonal contraceptives but are not on a stable dose of the same
                  hormonal contraceptive product for at least 4 weeks before dosing and who do not
                  agree to use the same contraceptive during the study or for 28 days after study
                  drug discontinuation.

               4. All females will be considered to be of childbearing potential unless they are
                  postmenopausal (amenorrheic for at least 12 consecutive months, in the
                  appropriate age group, and without other known or suspected cause) or have been
                  sterilized surgically (i.e, bilateral tubal ligation, total hysterectomy, or
                  bilateral oophorectomy, all with surgery at least 1 month before dosing).

          -  Alcohol dependency within 6 months before study entry

          -  Participant has a concurrent malignancy or malignancy within 3 years of enrollment,
             with the exception of adequately treated basal or squamous cell carcinoma,
             non-melanomatous skin cancer, or curatively resected cervical cancer.

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.