Letrozole reduces Ki67 in postmenopausal ER+/HER2- breast cancer after 7-30 days pre-surgery

This completed phase 2, non-therapeutic trial investigated the preoperative use of letrozole in postmenopausal women with newly diagnosed, operable, estrogen receptor-positive (ER+), HER2-negative breast cancer. The study enrolled 61 patients. The intervention involved a short, pre-surgical course of oral letrozole at a standard dose of 2.5 mg per day, administered for a duration of 7 to 30 days to accommodate variations in surgical scheduling. Definitive surgical resection (mastectomy or lumpectomy) was performed the day after the last letrozole dose, following standard of care guidelines. The study design included obtaining post-treatment tumor core needle biopsies (aiming for 4-6 cores) on the day of surgery, after the 7-30 days of letrozole treatment. Tissue was collected for both frozen and formalin-fixed analysis to be used for study-specific assays and routine histopathology. Whenever possible, these post-treatment biopsies were obtained intraoperatively by the surgeon. A tumor block from the surgical resection specimen was also collected. The primary outcome measure was the Ki67 index, specifically comparing its levels in highly hormone-dependent breast cancers versus those that are not. The study was led by the University of Texas Southwestern Medical Center, started on November 27, 2018, and had a primary completion date of February 24, 2025. Results were posted on March 16, 2026. The abstract does not report specific numerical results for the Ki67 index, safety signals, or study limitations.

If you're a postmenopausal woman just diagnosed with a common, hormone-sensitive type of breast cancer, your treatment plan might soon include a short, powerful step before surgery. This study looked at giving the drug letrozole for just 1 to 4 weeks before the scheduled operation to remove the tumor. The goal was to see if this brief pre-surgical treatment could slow down the cancer's growth in a meaningful way. Doctors took a small sample of the tumor with a needle biopsy at diagnosis. Then, after the patient took letrozole daily, they took another sample on the day of surgery to compare. The main thing they measured was a protein in the cancer cells called Ki67, which acts like a gauge of how fast the cells are dividing. By comparing the Ki67 levels before and after the letrozole course, researchers could see how much the drug affected the cancer's activity in a short time. This isn't meant to replace standard surgery or long-term therapy, but it gives doctors a real-time snapshot of how a patient's specific cancer responds to hormone-blocking treatment. Understanding this initial response could help inform decisions about further treatment after surgery.