Endocrine therapy, including aromatase inhibitor therapy, is the primary treatment for ER-positive metastatic disease. Despite the effectiveness of this treatment, not all patients respond to it and many patients who are initially responsive to the drug, eventually develop resistance to it. The management of patients with ER-positive, HER2-negative metastatic breast cancer who experience disease progression after standard treatment (CDK4/6 inhibitor plus an aromatase inhibitor) is a significant challenge and identification of new therapeutic strategies for this population of patients remains an unmet clinical need.~The aim of this research study is to determine if a month delay in the administration of the drug abemaciclib will be more effective than the drugs fulvestrant plus abemaciclib given together from the beginning for the treatment of ER-positive, HER2-negative metastatic breast cancer that has progressed on previous treatment. The study will investigate if a one month drug holiday from the CDK4/6 inhibitor drug, abemaciclib, will restore the body's sensitivity to the drug and make the subsequent treatment of abemaciclib plus fulvestrant more effective.~This study has two treatment groups. You will be assigned to either Group 1 or Group 2 based on computerized randomization or assignment. You will not be able to choose which group you will be in, but you will know your treatment group after randomization. Group 1 will receive abemaciclib and fulvestrant every 28 days. Group 2 will receive fulvestrant for 1 month, followed by abemaciclib and fulvestrant every 28 days.~The treatment will be administered until disease progression or unacceptable toxicity.
The study will investigate if a one month drug holiday from the CDK4/6 inhibitor drug, abemaciclib, will restore the body's sensitivity to the drug and make the subsequent treatment of abemaciclib plus fulvestrant more effective.