Inclusion Criteria for Dose Escalation:

          -  Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with
             evidence of either locally recurrent disease not amenable to resection or radiation
             therapy with curative intent or with metastatic disease

          -  ER-positive tumor

          -  HER2-negative breast cancer as per local laboratory testing

          -  Measurable disease, or evaluable bone disease; that is, bone lesions that are lytic or
             mixed (lytic + sclerotic) in the absence of measurable lesion

          -  Required paired pre- and on-treatment tumor biopsies for participants with metastases
             that are safely accessible as determined by the investigator

          -  Advanced or metastatic ER-positive/HER2-negative breast cancer that has recurred or
             progressed while being treated with adjuvant endocrine therapy for a duration of at
             least 24 months and/or endocrine therapy in the incurable, locally advanced, or
             metastatic setting and derived a clinical benefit from therapy (i.e., tumor response
             or stable disease for at least 6 months)

          -  No more than 2 prior lines of treatment for advanced or metastatic breast cancer

          -  ≥ 2 weeks must have elapsed from the use of any other endocrine, targeted therapy or
             chemotherapy

          -  Cohort B0: No prior treatment with Cyclin-Dependent Kinase (CDK) 4/6 inhibitor

          -  For participants undergoing 18F-fluoroestradiol (FES) positron emission tomography
             (PET) imaging additional restrictions on prior therapy include: ≥ 2 months must have
             elapsed from the use of tamoxifen; ≥ 6 months must have elapsed from the use of
             fulvestrant

          -  Postmenopausal status

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

          -  Resolution of all acute toxic effects of prior therapy or surgical procedures to
             baseline or Grade ≤ 1 (except alopecia or other toxicities not considered to be a
             safety risk for the patient)

          -  Life expectancy of ≥ 12 weeks

          -  Adequate organ function

        Inclusion Criteria for Dose Expansion:

        Same as above, except:

          -  No more than one prior line of treatment for advanced or metastatic breast cancer

          -  Advanced or metastatic disease that is either refractory to or intolerant of existing
             standard therapy or for which no effective standard therapy that confers clinical
             benefit is available

        And plus:

          -  Cohort B1−2: No prior treatment with CDK4/6 inhibitor

          -  Cohorts A1, A3, and B1 only: Postmenopausal status

          -  Cohorts A2, A4, and B2 only: Participants not defined as post-menopausal

          -  No prior treatment with an oral selective estrogen receptor degrader (SERD)

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use non-hormonal contraceptive methods with a failure
             rate of < 1% per year during the treatment period and for 40 days after the last dose
             of GDC-9545

        Exclusion Criteria for Dose Escalation:

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms.

          -  Current treatment with any systemic anti-cancer therapies for advanced disease

          -  Concurrent treatment with warfarin or phenytoin

          -  Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
             Stage I uterine cancer

          -  Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major
             upper GI surgery including gastric resection

          -  Known Human Immunodeficiency Virus (HIV) infection

          -  Known clinically significant history of liver disease consistent with Child-Pugh Class
             B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C
             virus), current alcohol abuse, or cirrhosis

          -  Major surgery within 4 weeks prior to enrollment

          -  Radiation therapy within 2 weeks prior to enrollment

        Exclusion Criteria for Dose Expansion:

        Same as above, plus:

          -  Pregnant, lactating, or breastfeeding

          -  Additional exclusion criteria for participants in Cohort B: History of venous
             thromboembolic event requiring therapeutic anticoagulation