A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors

Inclusion Criteria

1. Part 1: Breast Cancer (BC)
2. HR+, HER2- BC
3. Refractory HR-positive/HER2-positive BC
4. Part 1: Solid Tumors other than BC
5. Part 2:
6. HR-positive/HER2-negative BC
7. Lesion:
8. Part 1: evaluable lesion (including skin or bone lesion only)
9. Part 2: measurable lesion per RECIST v1.1
10. Prior systemic Treatment
11. Part 1: HR-positive/HER2-negative BC
12. At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease.
13. Prior chemotherapy in the metastatic setting is allowed.
14. Part 1: HR-positive/HER2-positive BC
15. At least 1 prior treatment of approved HER2 targeting therapy.
16. Part 1: Solid Tumors other than BC
17. Participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator.
18. Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET.
19. Parts 2B: At least 1 prior endocrine therapy for advanced or metastatic disease. Progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable.
20. Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed.

General Inclusion Criteria

21. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
22. Adequate renal, liver, and bone marrow function
23. Resolved acute effects of any prior therapy to baseline severity

Exclusion Criteria:

1. All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
2. Part 2B and 1C: Prior treatment with any CDK 4/6 inhibitor, or SERDs (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway for advanced disease.
3. Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
4. Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
5. Part 2C: Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
6. Part 2C: Any prior systemic treatment for advanced disease.
7. Prior irradiation to >25% of the bone marrow
8. Current use of drugs which have a risk for QTc prolongation
9. Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers

Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry

1. Participants with any other active malignancy within 3 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease
2. Major surgery within 4 weeks prior to study entry
3. Radiation therapy within 4 weeks prior to study entry.
4. Clinically important hypertension
5. Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)
6. Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed
7. Known active uncontrolled or symptomatic central nervous system (CNS) metastases
8. Active inflammatory GI disease
9. Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention
10. Previous high-dose chemotherapy requiring stem cell rescue
11. Participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

Other protocol specific exclusion criteria may apply