2026-04-14T08:44:16Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2148882026-03-07T01:06:55Zcom_2072_1057col_2072_478858col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Brasó Maristany, Fara author Ferrero Cafiero, Juan Manuel author Falato, Claudette author Martínez Sáez, Olga author Cejalvo, Juan Miguel author Margelí Vila, Mireia author Tolosa, Pablo author Salvador Bofill, Francisco Javier author Cruz, Josefina author González Farré, Blanca author Sanfeliu, Esther author Òdena, Andreu author Serra, Violeta author Pardo, Francisco author Luna Barrera, Ana María author Arumi, Miriam author Guerra, Juan Antonio author Villacampa, Guillermo author Sánchez Bayona, Rodrigo author Ciruelos, Eva author Espinosa Bravo, Martín author Izarzugaza, Yann author Galván, Patricia author Matito, Judit author Pernas, Sònia author Vidal, Maria author Santhanagopal, Anu author Sellami, Dalila author Esker, Stephen author Fan, Pang Dian author Suto, Fumitaka author Vivancos, Ana author Pascual, Tomás author Prat Aparicio, Aleix author Oliveira, Mafalda author 2024-08-30T14:50:09Z 2024-08-30T14:50:09Z 2024-07-11 2024-07-31T10:21:40Z Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.4 mg/kg (Part A), and 44 received a lower 5.6 mg/kg dose (Part B). The CelTIL score, measuring tumor cellularity and infiltrating lymphocytes from baseline to day 21, was used to assess drug activity. Part A demonstrated increased CelTIL score after one dose of HER3-DXd. Here we report CelTIL score and safety for Part B. In addition, the exploratory analyses of part A involve a comprehensive study of gene expression, somatic mutations, copy-number segments, and DNA-based subtypes, while Part B focuses on validating gene expression. RNA analyses show significant correlations between CelTIL responses, high proliferation genes (e.g., CCNE1, MKI67), and low expression of luminal genes (e.g., NAT1, SLC39A6). DNA findings indicate that CelTIL response is significantly associated with TP53 mutations, proliferation, non-luminal signatures, and a distinct DNA-based subtype (DNADX cluster-3). Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer. Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer. Càncer de mama Genètica mèdica Breast cancer Medical genetics Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response