16P Determinants of response to short preoperative endocrine therapy (pET) in hormone receptor-positive and HER2-negative (HR+/HER2-) early breast cancer (EBC)

pET in HR+/HER2- BC is a valuable tool for guiding treatment decisions, by offering real-time assessment of endocrine sensitivity. Changes in Ki67 induced by pET serve as a biomarker for assessing the need for adjuvant chemotherapy. We evaluated baseline clinicopathological and molecular features associated with Ki67 after short pET. A retrospective population-cohort involving 245 patients (pts) with HR+ HER2- EBC treated between 2014 and 2023 with pET for 2 to 12 weeks prior to surgery at the Hospital Clinic de Barcelona was analyzed. Data included age, stage, menopausal status (MS), body mass index (BMI), hormone receptors intensity, tumor infiltrate lymphocytes (TILS), PAM50 intrinsic subtype (IS) calculated by Prosigna, risk of recurrence (ROR), baseline and post treatment Ki67 and treatment strategies. pET response was defined as a complete cell cycle arrest (CCCA) (Ki67≤2.7%). Chi-square test, uni- and multi-variable logistic regression models identified variables associated with pET response. BMI, estrogen receptor, MS, baseline Ki67, TILs, ROR and IS were included in the multivariate analysis. Among 245 pts who underwent pET, with a median baseline Ki67 of 12% (1 – 80%), 47.6% reached CCCA. CCCA was significantly higher in postmenopausal than in premenopausal pts (56.3% vs 16.3%, p<0.001). According to IS, 44.1% (26) of Luminal A tumors had CCCA vs 26.5% in Luminal B (p=0.092), no non-luminal patients were identified. Regarding ROR, CCCA was reached in 50.0%(17), 37.5%(12) and 22.2%(6) of patients with low, intermediate and high risk, respectively (p=0.084). Higher baseline TILs were associated with lower CCCA (odds ratio OR=0.92; p=0.006). As for treatment, we found no differences in response by treatment duration, <4 vs 4 – 12 weeks (OR=1.16; p=0.729). Yet, tamoxifen did significantly worse than aromatase inhibitors, (OR=0.18; p<0.001). In the multivariable analysis, only IS (OR=10.31; p=0.046) was associated with CCCA, ROR as a continuous score was (OR=0.92; p= 0.040). IS and ROR are the strongest predictor of pET response. Combining these results with other risk assessment strategies could better individualize treatment strategies.