Abstract Background: Change in Ki67 expression between diagnostic biopsy and surgery of a breast cancer (BC) - the so-called window of opportunity - is commonly used as a surrogate marker of treatment response or to assess endocrine sensitivity as in the WSG-ADAPT HR+/HER2- trial. HRT-HC were shown to increase BC risk and are typically discontinued at BC diagnosis. Whether this withdrawal alone influences Ki67 dynamics remains unclear and may represent a potential confounding factor in the window of opportunity studies. Methods: This retrospective study included 382 female patients (pts) who underwent primary surgery at our breast center over a 4-year period (2020-2023). Clinical and tumor characteristics, including Ki67 levels at biopsy and surgery, were extracted from our institutional database. The primary objective was to compare the change in log Ki67 levels between the initial biopsy and the surgical specimen in pts with vs. without HRT-HC in HR+/HER2- BC (n=308). For this comparison, a linear regression adjusting for log Ki67 level at biopsy, HRT-HC use, age, menopausal status, year, stage, grade, expression levels of progesterone (PgR) and estrogen receptors, and histology was considered using the ratio of geometric means as an estimate of the effect of hormonal treatment. Results: Among patients with HR+/HER2- BC, 38% were premenopausal and 62% postmenopausal. At diagnosis, 27.9% of patients were receiving HRT-HC (39.3% of premenopausal and 20.9% of postmenopausal women). The distribution of Ki67 levels remained stable across the four years of assessment. Ki67 level was significantly correlated with the BC grade (1 vs. 2 vs. 3) and stage (I vs. II-III), at biopsy and at surgery. The correlation with menopausal status was significant only at surgery. No correlation was observed with PgR vs. 20%. Median time from biopsy to surgery was 39 days. Ki67 level was 9.2% lower at surgery than at biopsy (p=0.025). There was no significant difference in terms of Ki67 level at biopsy in pts with HRT-HC vs. without. However, the geometric mean of Ki67 at surgery for pts with HRT-HC was 29% lower than for pts without HRT-HC, adjusted for Ki67 level at biopsy (p=0.007). They also had a higher likelihood to present a Ki67 level 10% at surgery (estimate 0.52, p=0.015). This difference stayed significant in multivariable analysis (p0.001). Conclusion: HR+/HER2- BC pts who interrupt HRT-HC upon BC diagnosis present a statistically significant drop in Ki67 level between diagnostic biopsy and surgery; a change which is not observed in patients HRT-HC naive. A significantly higher proportion of pts with HRT-HC also achieved a Ki67 level below 10% at surgery, a commonly used cutoff for decision. Thus, HRT-HC may act as a confounder factor when administrating a window of opportunity treatment to guide adjuvant systemic treatment or to predict a treatment efficacy based on Ki67 levels. These findings and their potential clinical relevance warrant validation in a larger multicenter cohort. Citation Format: L. Fontannaz, J. Sauser, B. Bisig, N. Dris, A. Kakourou, B. Giacomuzzi-Moore, A. Stravodimou, A. Liapi, C. Perrinjaquet, A. Dolcan, B. Wolf, E. Dubruc, D. Hastir, K. Zaman. Ki67 change between diagnostic biopsy and surgery: impact of hormonal replacement therapy or contraception (HRT-HC) withdrawal at breast cancer diagnosis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-07-01.
Fontannaz et al. (2026) studied this question.