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

This study is a randomized, open-label, phase II trial designed to evaluate whether alternate-day dosing of letrozole preserves antiproliferative activity compared with standard daily dosing in postmenopausal women with estrogen receptor-positive, HER2-negative breast cancer.

Inclusion Criteria: * Participants must have histologically confirmed breast cancer, clinical stage I-III as per the AJCC 8th edition (Anatomic Prognostic Staging). Tumors must be estrogen receptor-positive (ER expression ≥ 10%) and HER2 negative (IHC 0-1+, or IHC 2+ with negative FISH). Tumors can be progesterone receptor positive or negative. Participants must be planned to undergo surgery upfront. Age ≥18 years. Participants must be postmenopausal female. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A). Participants must have an adequate organ and marrow function as defined below: absolute neutrophil count ≥1,000/mcL platelets ≥100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN creatinine ≤ institutional ULN Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. Participants must not have received prior therapy for current breast cancer. Participants must be postmenopausal defined as any of the following: * Age ≥60 years * Age \