Ki67 dynamic predicts endocrine sensitivity in estrogen receptor-positive/ HER2-negative breast cancer patients undergoing preoperative endocrine therapy

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dc.catalogadorjlo
dc.contributor.authorGómez-Bravo, R.
dc.contributor.authorWalbaum, B.
dc.contributor.authorBergamino, M.
dc.contributor.authorMartínez-Sáez, O.
dc.contributor.authorSchettini, F.
dc.contributor.authorSeguí, E.
dc.contributor.authorGarcía-Fructuoso, I.
dc.contributor.authorPascual, T.
dc.contributor.authorChic, N.
dc.contributor.authorGonzález, M.
dc.contributor.authorRodríguez, A.
dc.contributor.authorRey, M.
dc.contributor.authorGiménez-Xavier, P.
dc.contributor.authorBlasco, P.
dc.contributor.authorCastillo, O.
dc.contributor.authorGalván, P.
dc.contributor.authorSanfeliu, E.
dc.contributor.authorGonzález-Farré, B.
dc.contributor.authorVidal, M.
dc.contributor.authorAdamo, B.
dc.contributor.authorBrasó-Maristany, F.
dc.contributor.authorPrat, A.
dc.contributor.authorMuñoz, M.
dc.date.accessioned2025-10-23T18:28:09Z
dc.date.available2025-10-23T18:28:09Z
dc.date.issued2025
dc.description.abstractBackground: Early decrease in Ki67 after a short preoperative course of endocrine therapy (ET) has shown prognostic and predictive value in clinical research, but its applicability and reproducibility in routine clinical practice remain largely unknown. We therefore assessed on-treatment Ki67 changes following a short preoperative ET and its association with biological variables, such as intrinsic subtype and risk of recurrence (ROR), plus long-term outcomes, in a real-world cohort of patients with early estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-negative) breast cancer. Methods: We conducted a retrospective, registry-based analysis of 230 consecutive patients with early ER+/HER2− breast cancer treated as per standard clinical care at the Breast Unit of the Clinic Barcelona Comprehensive Cancer Center between 2014 and 2023. All patients received preoperative ET, tamoxifen, or an aromatase inhibitor (AI), for 2-12 weeks before surgery. Clinical and pathological variables were collected and stratified by Ki67 response: “responders” (post-treatment Ki67 0% to 10%) and “complete cell cycle arrest (CCCA) responders” (Ki67 ≤2.7%). PAM50/Prosigna was used to determine intrinsic subtypes and ROR-score. Event-free survival was estimated using Kaplan—Meier curves, and associations were tested using Cox proportional hazards regression. Results: The median duration of preoperative ET was 5 weeks (min-max range, 2-12 weeks). Overall, 196 patients (85.2%) met the Ki67 response criterion and 111 (48.3%) achieved CCCA. Response rates were significantly higher in postmenopausal compared with premenopausal women (P = 0.004). Notably, 95.6% of postmenopausal patients received an AI, whereas all premenopausal women were treated with tamoxifen. Additionally, response varied by intrinsic subtype, favoring Luminal A tumors (P = 0.047). In multivariable models, postmenopausal status and higher baseline ER expression were independently associated with both Ki67 response and CCCA, whereas a lower baseline ROR-score predicted CCCA. After a median follow-up of 47 months, CCCA was associated with significantly improved event-free survival [hazard ratio (HR) = 0.19; 95% CI (confidence interval) 0.05-0.72; P value = 0.012]. Conclusion: In routine practice, a short course of preoperative ET yields substantial reductions in tumor proliferation. Early assessment of Ki67 suppression offers a readily accessible indicator of endocrine sensitivity, and achieving CCCA identifies patients who have a more favorable prognosis and thus are potentially eligible to de-escalate in treatment strategies.
dc.format.extent9 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.esmoop.2025.105845
dc.identifier.issn2059-7029
dc.identifier.urihttps://doi.org/10.1016/j.esmoop.2025.105845
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/106335
dc.information.autorucEscuela de Medicina; Walbaum García, Benjamín Vicente; 0000-0003-2314-5360; 163702
dc.issue.numero11
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaESMO Open
dc.rightsacceso abierto
dc.rights.licenseCC BY-NC-ND 4.0 Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectPreoperative endocrine therapy
dc.subjectKi67
dc.subjectComplete cell cycle arrest
dc.subjectDynamic biomarkers
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleKi67 dynamic predicts endocrine sensitivity in estrogen receptor-positive/ HER2-negative breast cancer patients undergoing preoperative endocrine therapy
dc.typeartículo
dc.volumen10
sipa.codpersvinculados163702
sipa.trazabilidadORCID;2025-10-20
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