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

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07220060 and PF-07104091) in people with breast cancer. This clinical study consists of 2 parts (part 1 and part 2). In part 1, we are seeking participants who:

* Have been diagnosed with Breast Cancer (BC) of either types:
* Have HR+, HER2- BC
* Refractory HR-positive/HER2-positive BC
* Have other solid tumors other than BC

In part 2, we are seeking participants who:

-Have HR-positive/HER2-negative BC Part 1 will include increasing doses of PF-07220060 with PF-07104091. In part 2, participants will take 1 of 2 study medicine combinations. This will help us decide the highest amount of study medicines that can be safety given to people. All participants in this study will receive PF-07220060 with PF-07104091 by mouth. We will compare participant experiences to help us determine if PF-07220060 with PF-07104091 is safe and effective. Participants will take part in this study for about 2 years. During this time, they will receive the study medicine, an x-ray imaging, and will be observed for safety and effects of the study medicines.


Eligibility Criteria:
Inclusion Criteria

* Part 1: Breast Cancer (BC)
* HR+, HER2- BC
* Refractory HR-positive/HER2-positive BC
* Part 1: Solid Tumors other than BC
* Part 2:
* HR-positive/HER2-negative BC
* Lesion:
* Part 1: evaluable lesion (including skin or bone lesion only)
* Part 2: measurable lesion per RECIST v1.1
* Prior systemic Treatment
* Part 1: HR-positive/HER2-negative BC
* At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease.
* Prior chemotherapy in the metastatic setting is allowed.
* Part 1: HR-positive/HER2-positive BC
* At least 1 prior treatment of approved HER2 targeting therapy.
* Part 1: Solid Tumors other than BC
* 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.
* Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET.
* 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.
* Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed.
* General Inclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* Adequate renal, liver, and bone marrow function
* Resolved acute effects of any prior therapy to baseline severity

Exclusion Criteria:

* All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
* 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.
* Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
* Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
* 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.
* Part 2C: Any prior systemic treatment for advanced disease.
* Prior irradiation to \>25% of the bone marrow
* Current use of drugs which have a risk for QTc prolongation
* 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

  * 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
  * Major surgery within 4 weeks prior to study entry
  * Radiation therapy within 4 weeks prior to study entry.
  * Clinically important hypertension
  * Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)
* Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed
* Known active uncontrolled or symptomatic central nervous system (CNS) metastases
* Active inflammatory GI disease
* Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention
* Previous high-dose chemotherapy requiring stem cell rescue
* 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