Browsing by Author "Castillo, O."

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    Ki67 dynamic predicts endocrine sensitivity in estrogen receptor-positive/ HER2-negative breast cancer patients undergoing preoperative endocrine therapy
    (2025) Gómez-Bravo, R.; Walbaum, B.; Bergamino, M.; Martínez-Sáez, O.; Schettini, F.; Seguí, E.; García-Fructuoso, I.; Pascual, T.; Chic, N.; González, M.; Rodríguez, A.; Rey, M.; Giménez-Xavier, P.; Blasco, P.; Castillo, O.; Galván, P.; Sanfeliu, E.; González-Farré, B.; Vidal, M.; Adamo, B.; Brasó-Maristany, F.; Prat, A.; Muñoz, M.
    Background: 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.
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    Mediterranean food and diets, global resource for the control of metabolic syndrome and chronic diseases.
    (2008) Urquiaga, I.; Echeverría, G.; Polic, G.; Castillo, O.; Liberona, Y.; Rozowski, J.; Perez, D.; Martinez, C.; Vasquez, L.; Strobel, P.; Mezzano, D.; Leighton, F.
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    Prenatal growth and metabolic syndrome components among Chilean children
    (CAMBRIDGE UNIV PRESS, 2012) Mardones, F.; Villarroel, L.; Arnaiz, P.; Barja, S.; Dominguez, A.; Castillo, O.; Farias, M.; Eriksson, J. G.; Pacheco, P.
    The association of prenatal growth with metabolic syndrome (MS) components and insulin resistance (IR) in children has not been studied in Chile and most developing countries. Some associations found in developed countries are controversial. A retrospective cohort study was designed linking present information on MS components and IR in children with register-based information on birth weight (BW), birth length (BL) and gestational age (GA). Examinations included anthropometry and blood pressure (BP), as well as self-report of pubertal status. A fasting blood sample was taken to determine lipids, glucose, insulin and homeostasis model assessment (HOMA)-IR was calculated. The study cohort of 2152 children was on average 11.4 +/- 1.0 years old. The prevalence of MS, IR and overweight were 7.6%, 24.5% and 34%, respectively. Elevated BP was negatively associated with dichotomized risk categories of the perinatal factors studied (BW, BL and GA). Contingency tables showed that high waist circumference (WC) and elevated BP had a U-shaped association with various categories of BW and BL, respectively. Stepwise linear regressions selected: (a) WC as inversely associated to GA and directly associated to BW, (b) BP as inversely associated to GA and (c) HOMA-IR as inversely associated to BL. Non-optimal prenatal growth seems to predispose to high WC, elevated BP and IR in school-age children, supporting the early life origin of several non-communicable diseases. Those associations were rather weak as estimated by the slopes of the regressions and probably reduced by their U-shaped nature; they would reasonably become stronger with a longer follow-up.