The purpose of this study is to determine whether an experimental drug called AZD9833 is better at treating breast cancer characterized by the development of an ESR1 mutation than the standard of care (SoC) combination of an aromatase inhibitor and a CDK4/6 inhibitor.

An experimental drug is one that is being tested and is not yet approved by the United States Food and Drug Administration (FDA).

Over time, ESR1 mutations may make it more likely that the cancer will decrease the effectiveness of the standard of care medications, which could lead to the cancer growing back or getting worse. AZD9833 is a medicine taken by mouth that stops some of the actions of estrogen, which may have an effect on the growth of breast cancer. It is also a hormonal therapy and  belongs to a group of drugs called selective estrogen receptor degraders (SERDs). 

There are two parts to this study. Step 1 consists of tests and procedures intended to identify ESR1 mutations. Step 2 will take place once an ESR1 mutation is identified in blood samples and consists of taking the study drug, AZD9833. 

Participants will be randomized into one of two groups. Randomization is like flipping a coin and there is a 50/50 chance of being assigned to either group. One group will receive AZD9883 and the other will continue to receive the standard of care.