De-EscaLaTion of Aromatase Inhibitor Therapy: A Randomized Phase II Study of De-escalated Letrozole in Hormone Receptor-Positive Early Breast Cancer

The objective of the study is to determine whether alternate-day dosing maintains suppression of tumor proliferation comparable to standard daily dosing. This study is designed to evaluate a dose de-escalation strategy using alternate-day letrozole dosing in patients with hormone receptor-positive breast cancer. By assessing short-term changes in Ki-67 following treatment, this study will determine whether reduced dosing maintains antiproliferative activity comparable to standard daily therapy. Demonstrating similar suppression of tumor proliferation with alternate-day dosing would provide important biological evidence that reduced-dose endocrine therapy may maintain therapeutic activity while potentially improving tolerability. Such findings could support the development of future strategies aimed at optimizing endocrine therapy dosing, improving patient adherence, and ultimately enhancing long-term outcomes for patients with hormone receptor-positive breast cancer. In addition, this study will generate important translational data regarding the relationship between endocrine therapy dosing, systemic estrogen suppression, lipid profile panel, and tumor proliferation. By integrating tumor-based biomarkers with pharmacodynamic measurements, the study seeks to better understand whether reduced-dose aromatase inhibition can achieve similar biological effects as standard dosing. If successful, this approach could inform future clinical trials evaluating endocrine therapy optimization and may contribute to more individualized endocrine treatment strategies for patients with hormone receptor-positive breast cancer.