Strategies for utilizing Ki67 and multigene assays as a window of opportunity in the treatment of HR+/HER2– early breast cancer in clinical practice
Authors:
doc. MUDr. Bielčiková Zuzana; Ph. D 1,2; MUDr. Zimovjanová Martina, Ph.D.; Mha 1; MUDr. Kindl Jan 1
Authors‘ workplace:
Onkologická klinika 1. LF UK a VFN v Praze
1; Onkologická ambulance, Nemocnice na Františku, Praha
2
Published in:
Klin Onkol 2026; 39(4): 266-275
Category:
Original Articles
doi:
https://doi.org/10.48095/ccko2026266
Overview
Introduction: Window of Opportunity (WoO) is a strategy for testing tumor sensitivity to endocrine therapy (ET) by comparing proliferative activity (Ki-67) before treatment (from a biopsy) and after short-term ET (from a surgical specimen). In addition to standard clinicopathological parameters and multigene assays (MGAs), WoO represents an additional prognostic marker for assessing recurrence risk in early luminal breast cancer. Here, we report partial results of a study focused on the practical implementation of the WoO strategy in routine clinical practice. Methods: This is a prospective, non-randomized academic study initiated in January 2025 at the General University Hospital in Prague. Patients with early luminal breast cancer indicated for primary surgical treatment were offered short-term preoperative ET in the form of an aromatase inhibitor (AI), tamoxifen (TMX), or a combination of TMX or AI with an LHRH analogue for 10–30 days. The primary objective of the study was to establish a workflow for incorporating the WoO strategy into clinical practice, to develop a protocol for the indication of preoperative ET, and to create a protocol for evaluating Ki-67 dynamics alongside standard clinicopathological parameters, and when applicable, MGA results. Results: Between January 1, 2025 and December 31, 2025, a total of 49 women were enrolled, with a median age of 59 years; 15 were premenopausal. The median duration of preoperative ET was 21 days. Patients were stratified into low-clinical risk (C_low; group 1, N = 29) and high-clinical risk (C_high; group 2, N = 20) categories according to Adjuvant! Online. The aggressiveness of clinicopathological parameters correlated with clinical risk and treatment response (no statistical analysis was performed). Proportion of responders (RES), defined as patients demonstrating a decrease in Ki-67 within the WoO strategy, was higher among patients with C_low disease. MGA testing was performed in 11 patients and had the greatest relevance in the C_high group. Contribution of the WoO strategy to adjuvant treatment decision-making was highest among RES. Replacement of MGA by the WoO strategy requires further validation; the greatest potential appears to be in C_low patients with a concomitant decrease in Ki-67. The need for adjuvant chemotherapy in non-responders (non-RES) with C_low disease requires further investigation. Conclusion: The WoO strategy assists in assessing recurrence risk and guiding adjuvant therapy decisions. The study continues with the enrollment of patients with a higher baseline Ki-67 at diagnosis.
Keywords:
early luminal breast cancer – Window of Opportunity – Ki-67 – multigene assays – adjuvant therapy, prognosis
Sources
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