• ER-, PR-, HER2- TNBC
• Clinical stage either
  • T2-T4, N0, M0 or
  • T1-T3, N1-2, M0
  • No T4/N+, any N3, or inflammatory breast cancer
• No prior systemic therapy for curative intent
• No previous ipsilateral surgery for current breast surgery
• ECOG PS 0-

Inclusion Criteria:

• Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without evidence of distant metastasis.
• Participants must have received at least 24 months but not more than 60 months of any adjuvant ET, from time of adjuvant ET initiation.
• Participants may have received (neo) adjuvant chemotherapy and/or targeted therapy with a CDK4/6- or PARP- inhibitor.
• Must have an increased risk of disease recurrence based on clinical-pathological risk features.
• Have a Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group scale.
• Have adequate organ function.

Exclusion Criteria:

• Have any evidence of metastatic disease (including contralateral ALN) or inflammatory breast cancer at primary breast cancer diagnosis.
• Participants with more than a 6-month consecutive gap in therapy during the course of prior adjuvant ET.
• Participants who have completed or discontinued prior adjuvant ET >6 months prior to screening.
• Participants with a history of previous breast cancer are excluded, with the exception of ipsilateral DCIS treated by locoregional therapy alone ≥5 years ago.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study intervention.
• Participant has previously received ET of any duration for breast cancer prevention (tamoxifen or AIs) or raloxifene.
• Participants with a history of any other cancer.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study.

• Premenopausal
  • Age 40 years or under with spontaneous menses within 12 months
  • Age 50-60 years with spontaneous menses within 12 months plus FSH and estrodiol measurements within premenopausal range
  • Amenorrhea due to IUD or uterine ablation or hysterectomy must have FSH and estrodiol ranges in premenopausal range
• ECOG PS 0-2
• Multicentric or multifocal breast cancer is allowed
• Must have had definitive breast surgery (+radiation if indicated)
• Primary tumor must be T1-3
• Nodes must be N0 or N1
• Oncotype score must be,
  • if node negative: 21-25 or high clinical risk (with oncotype 16-20)
  • If 1-3 nodes, must be <26
• Must be ER/PR positive
• Must be HER2 negative
• No metastatic disease

Inclusion Criteria:

• Histologically confirmed invasive breast carcinoma
• Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer
• Centrally confirmed PD-L1 and hormone receptor status
• Clinical stage at disease presentation (prior to neoadjuvant therapy): cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (participants with cT1mi/T1a/T1b/N0 are not eligible)
• Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are permitted)
• <=12 weeks between primary surgery and randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Screening left ventricular ejection fraction (LVEF) >= 50% and no decrease in LVEF by >15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF >= 55%
• Life expectancy >= 6 months
• Adequate hematologic and end organ function

Exclusion Criteria:

• Stage IV breast cancer
• An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy
• Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors
• History of exposure to various cumulative doses of anthracyclines
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or ductal carcinoma in situ (DCIS)
• Current grade >=2 peripheral neuropathy
• History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis
• History of or active autoimmune disease or immune deficiency
• Treatment with immunostimulatory or immunosuppressive agents
• Cardiopulmonary dysfunction
• Any known active liver disease

• Histologically confirmed TNBC, Stage I-III
• Residual invasive disease in the breasat and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy
• Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without carboplatin, with or without pembrolizumab
• No evidence of locoregional or distant relapse
• Surgical removal of all clinically evident disease
• ECOG PS 0-1
• No adjuvant systemic therapy
• LVEF > 50%
• No known germline BRCA mutation
• No Stage IV disease
• No history of prior invasive breast cancer
• No persistent toxicities from prior anticancer therapies
• No prior autoimmune or inflammatory disorders
• No known HIV

• Metastatic or locally advanced breast cancer not amenable to treatment with curative intent
• ER+, HER2-
• Prior endocrine therapy in combination with CDK 4/6 in either metastatic setting with disease progression after 6 months or in the adjuvant setting with relapsed disease within 12 months of exposure. (patients must have taken at least 12 months of adjuvant endocrine therapy, of which 6 months were in combination with a CDK4/6 inhibitor)
• Measurable disease or evaluable bone mets
• ECOG PS 0-1
• For premenopausal or perimenopausal women or men must have treatment with LHRH agonist therapy for duration of study
• No prior treatment with oral SERD, SERM, or everolimus. Fulvestrant is allowed if tx stopped at least 28 days prior to randomization
• No more than 2 prior lines of systemic endocrine therapy in metastatic setting
• No prior chemotherapy in metasatic setting
• No other malignancy within 5 years except nonmelanoma skin cancer, papillary thyroid cancer, or very low risk of recurrence cancers
• No known active CNS mets

• Locally advanced or metastatic adenocarcinoma of the breast
• Documented ER positive, HER2 negative
• Confirmed ESR mutation status through central lab testing
• Resistance to prior adjuvant endocrine therapy
• No prior systemic anti-cancer therapy for advanced disease
• Prior use of adjuvant CDK4/6 inhibitor is allowed
• No prior treatment with another SERD (e.g. fulvestrant)
• No active cardiac disease

• Histologically or cytologically confirmed and documented human epidermal growth factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection
• Evaluable disease (measurable not required)
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of ≥6 months
• ECOG PS 0-1
• LVEF of at least (≥)50%
• No previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
• No prior treatment with a selective estrogen receptor degrader (SERD)
• No previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
• No disease progression within 6 months of receiving trastuzumab, with or without pertuzumab, or ado-trastuzumab emtansine in the adjuvant setting
• No history of exposure to the following cumulative doses of anthracyclines; Doxorubicin >360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.
• No known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
• No current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
• No history of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death

• Triple negative metastatic breast cancer
• 2nd line
• ECOG PS 0-2
• No prior treatment with any study agents
• No history of autoimmune disease
• Presence of measurable disease
• No symptomatic or untreated CNS disease

• ER+, Her2 negative breast cancer
• Endocrine therapy recommended, cytotoxic chemotherapy not recommended
• Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease (note: at least one line of therapy must have contained a CDK4/6i administered for a minimum of 8 weeks prior to disease progression.)
• Postmenopausal status 
• ECOG 0-1
• Available tumor specimen
• Prior fulvestrant therapy is allowed
• Measurable disease
• No prior cytotoxic chemotherapy for metastatic disease
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

• Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumors
• Must have tumor specimen available
• Measurable disease
• ECOG PS 0-1
• Life expectancy at least 12 weeks
• Phase 1a- must have exhausted all standard therapies for their disease
• Phase 1b- must have disease that has progressed after at least one available standard therapy
• Some cohorts are tumor-type specific- please contact study team to see if tumor type is eligible at any time during the study
• No active HBV/HCV or chronic or acute EBV
• No history of autoimmune disease
• No symptomatic or actively progressing CNS mets