Título:
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Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer
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Autor/a:
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Lopez-Bonet, Eugeni; Buxó, Maria; Cuyàs, Elisabet; Pernas, Sonia; Dorca, Joan; Álvarez, Isabel; Cortés Castan, Javier
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Otros autores:
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Institut Català de la Salut; [Lopez-Bonet E] Department of Anatomical Pathology, Dr. Josep Trueta Hospital of Girona, Girona 17005, Spain. [Buxó M] Girona Biomedical Research Institute (IDIBGI), Girona 17190, Spain. [Cuyàs E] Girona Biomedical Research Institute (IDIBGI), Girona 17190, Spain. Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona 08908, Spain. [Pernas S] Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona 08908, Spain. [Dorca J] Medical Oncology, Catalan Institute of Oncology, Girona 17005, Spain. [Álvarez I] Medical Oncology Service, Hospital Universitario Donostia, Donostia-San Sebastián 20014, Spain. Biodonostia Health Research Institute, Donostia-San Sebastián 20014, Spain. [Cortés J] IOB Institute of Oncology, Hospital Quirónsalud, Madrid & Barcelona 08023, Spain. Medica Scientia Innovation Researcher (MedSIR), Barcelona 08007, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Hospital Universitari Vall d'Hebron |
Abstract:
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Metformina; Ki67; Càncer de mama |
Abstract:
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Metformina; Ki67; Cáncer de mama |
Abstract:
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Metformin; Ki67; Breast cancer |
Abstract:
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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. |
Abstract:
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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). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. |
Materia(s):
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-Metformina -Mama - Càncer -DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms -Other subheadings::Other subheadings::Other subheadings::/drug therapy -ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama -Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia |
Derechos:
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Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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MDPI
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