Dynamics of morphological and immunohistochemical parameters during preoperative hormone sensitivity testing in patients with luminal HER2-negative breast cancer

Background. Breast cancer (BC) is a heterogeneous disease that presents significant challenges in treatment planning. A short-term preoperative test for hormone sensitivity (THS) is one approach to personalizing adjuvant systemic therapy for patients with BC. Despite its availability for over 25 years, several unresolved issues continue to limit the widespread adoption of test hormone therapy in clinical practice. Aim. To evaluate changes in morphological and immunohistochemical parameters during preoperative THS in patients with luminal HER2-negative BC and to identify factors influencing these changes. Materials and methods. The study cohort comprised 254 patients with luminal HER2-negative BC treated at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology between 2018 and 2024. During the preoperative stage, core biopsies of breast tumors were obtained, followed by administration of short-term THS. Premenopausal patients received tamoxifen with or without ovarian suppression using goserelin, while postmenopausal patients received aromatase inhibitors. Post-surgical assessment included evaluation of changes in tumor proliferative activity, as measured by degree of malignancy (G) and Ki67 levels, as well as changes in estrogen receptor (ER) and progesterone receptor (PR) expression in surgical specimens. Results. Following short-term THS, a statistically significant decrease was observed in the expression of ER (p0.001), PR (p0.001), Ki67 (p0.001), and degree of malignancy (p=0.031). Multivariate regression analysis identified baseline Ki67 (p0.001), drug type (p=0.012), and ER expression (p=0.012) as significant predictors of Ki67 reduction. Conclusion. Alterations in hormone receptor expression, Ki67, and degree of malignancy during preoperative THS facilitate prediction of clinical response and assessment of endocrine therapy effectiveness in vivo within a short timeframe. This approach may allow some patients to avoid unnecessary and highly toxic chemotherapy.