2026-04-17T17:29:51Zhttps://recercat.cat/oai/request
oai:recercat.cat:10256/182932024-06-18T12:41:11Zcom_2072_452955com_2072_2054col_2072_453079
RECERCAT author López Bonet, Eugeni author Buxó Pujolràs, Maria author Cuyàs, Elisabet author Pernas, Sonia author Dorca, Joan author Álvarez, Isabel author Martínez, Susana author Pérez Garcia, Jose Manuel author Batista López, Norberto author Rodríguez Sánchez, César A. author Amillano, Kepa author Domínguez, Severina author Luque, Maria author Morilla, Idoia author Stradella, Agostina author Viñas, Gemma author Cortés, Javier author Oliveras, Glòria author Meléndez Frigola, Cristina author Castillo, Laura author Verdura, Sara author Brunet i Vidal, Joan author Joven, Jorge author Garcia, Margarita author Saidani, Samiha author Martin Castillo, Begoña author Menéndez Menéndez, Javier Abel 2024-06-18T12:41:11Z 2024-06-18T12:41:11Z 2019-12-11 http://hdl.handle.net/10256/18293 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: This work was supported by Grants from the Ministerio de Sanidad, Servicios Sociales e Igualdad (EC10-125, Ayudas para el Fomento de la Investigación Clínica Independiente to Begoña Martin-Castillo). Work in the Menendez laboratory is supported by the Spanish Ministry of Science and Innovation (Grant SAF2016-80639-P, Plan Nacional de l+D+I, founded by the European Regional Development Fund, Spain) and by an unrestricted research grant from the Fundació Oncolliga Girona (Lliga catalana d’ajuda al malalt de càncer, Girona) Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Metformina Metformin Mama -- Càncer -- Tractament Breast -- Cancer -- Treatment Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed