Real-World Feasibility Assessment of Short-Course Preoperative Endocrine Therapy Using the Ki67 Biomarker in an...

Preoperative endocrine therapy (ET) can be used in the lead-up to surgery in estrogen receptor positive (ER+) early breast cancer (eBC), without delaying surgery. Preoperative ET (pET) may not yield clinically significant tumor shrinkage, unlike conventional neoadjuvant treatment. However, dynamic Ki67 changes with pET can provide biological tumor response information, akin to genomic recurrence assays, in post- and pre/perimenopausal patients. We aimed to assess pET feasibility in an Australian ER+/HER2- eBC cohort.

Single-center retrospective study of ER+/HER2- eBC patients who received pET from December 2022 to June 2025. Demographic, oncological, and pathological data were collected. pET response was defined as surgical excisional Ki67_low ≤ 10%.

Overall, 102 patients (85.3% postmenopausal) were prescribed pET, median age 65 years (interquartile range [IQR] 58.3-73.8). Thirty-nine patients (38.2%) underwent mastectomy, and 36 patients (33.6%) had node positive disease. Median time between pET commencement and surgery was 29 days (IQR 16.3-42.0). Eighty-six patients (84.3%) demonstrated excisional Ki67_low ≤ 10% on pET, including 12 pre-menopausal patients (80.0%). Importantly, 45 pET responders (47.4%) demonstrated conversion from core biopsy (CBx) Ki67_high > 10% to surgical Ki67_low ≤ 10%. Median Ki67 value from baseline CBx to surgery declined on pET (15.0% vs. 5.0%). Most patients (n = 76, 74.5%) received adjuvant ET alone.

The majority of patients in this cohort were endocrine sensitive. A significant proportion of the cohort demonstrated Ki67_high to Ki67_low conversion, which may be a clinically meaningful measure of endocrine response on pET. Prospective validation is required to link pET response to clinical outcomes and adjuvant treatment decisions.