2026-04-13T01:11:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2165592025-12-05T12:29:37Zcom_2072_1057col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Fullana, Bartomeu author Morales, Serafín author Petit, Anna author Alay, Ania author Verdaguer, Helena author Climent, Fina author Navarro Perez, Valentí author Cejuela, Mónica author Galvan, Patricia author Gumà, Anna author Llombart Cussac, Antonio author Cordero, David author Casanovas, Oriol author Prat Aparicio, Aleix author Gil Gil, Miguel author Pernas, Sònia author 2024-11-18T12:31:58Z 2024-11-18T12:31:58Z 2024-10-09 2024-11-18T12:22:56Z Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2- stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4-5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009 Càncer de mama Terapèutica Breast cancer Therapeutics Neoadjuvant sunitinib plus exemestane in post-menopausal women with hormone receptor-positive/HER2-negative early-stage breast cancer (SUT_EXE-08): a phase I/II trial