Abstract Even though most women with estrogen receptor positive (ER+) breast tumors can benefit from endocrine therapy (ET), up to 40% of these patients will eventually experience relapse. Moreover, when these tumors recur, they tend to be more metastatic and therapy-resistant, resulting in disease progression and fatalities. One contributing factor to ET failure and recurrence is intratumoral heterogeneity, where tumors have distinct populations of cells with different sensitivity to ET. Here,