Autor según el artículo: Lopez-Bonet E, Buxó M, Cuyàs E, Pernas S, Dorca J, Álvarez I, Martínez S, Pérez-Garcia JM, Batista-López N, Rodríguez-Sánchez CA, Amillano K, Domínguez S, Luque M, Morilla I, Stradella A, Viñas G, Cortés J, Oliveras G, Meléndez C, Castillo L, Verdura S, Brunet J, Joven J, Garcia M, Saidani S, Martin-Castillo B, Menendez JA
Departamento: Medicina i Cirurgia
Autor/es de la URV: Joven Maried, Jorge
Palabras clave: Residual disease Metformin Ki67 Breast cancer
Resumen: The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (?20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.
Áreas temáticas: Medicine, general & internal Medicine (miscellaneous) Medicine (all)
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 20770383
Direcció de correo del autor: jorge.joven@urv.cat
Identificador del autor: 0000-0003-2749-4541
Fecha de alta del registro: 2023-02-18
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.mdpi.com/2077-0383/8/12/2180
URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Journal Of Clinical Medicine. 8 (12):
Referencia de l'ítem segons les normes APA: Lopez-Bonet E, Buxó M, Cuyàs E, Pernas S, Dorca J, Álvarez I, Martínez S, Pérez-Garcia JM, Batista-López N, Rodríguez-Sánchez CA, Amillano K, Domíngue (2019). Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer.. Journal Of Clinical Medicine, 8(12), -. DOI: 10.3390/jcm8122180
DOI del artículo: 10.3390/jcm8122180
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2019
Tipo de publicación: Journal Publications
Repositori URV