A Study to Learn About the Study Medicine PF-07220060 Together With Letrozole Compared to Letrozole Alone in Women Post Menopause

The purpose of this study is to learn about the effects of the study medicine PF-07220060 plus letrozole, compared with the effects of taking letrozole alone without PF-07220060 for treatment of breast cancer.

This study is seeking for participants who are:

* women of age 18 years and older post menopause (either naturally or surgically).
* confirmed to have Hormone receptor (HR) positive, Human epidermal growth factor receptor 2 (HER2) negative breast cancer. HER2 negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface.
* not been treated for their cancer before this study.

Participants will be randomly assigned (like flipping a coin) to receive the treatment (PF-07220060 plus letrozole) or letrozole alone. Both PF-07220060 and letrozole are taken by mouth. PF-07220060 will be taken twice a day for 14 days. Letrozole will be taken once a day for 14 days.

Participants will have a screening period for up to 28 days. If deemed fit, they will receive study treatment for 14 days, and then will have a follow-up visit about 28 days after their last dose.

All participants will have at least one biopsy during the study. Biopsy is the removal of cells or tissues for examining. All participants will have a biopsy on Day 14.

Additional assessments for safety including blood draws and interviews done by the site staff will be completed during the study.