Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer

Autor: Sara Verdura, Agostina Stradella, Gemma Viñas, Jorge Joven, N. Batista-López, Cristina Meléndez, Margarita Garcia, Susana Martínez, Elisabet Cuyàs, Joan Dorca, Samiha Saidani, M. Luque, Maria Buxó, Javier A. Menendez, César A Rodríguez-Sánchez, Sonia Pernas, Severina Domínguez, Glòria Oliveras, Kepa Amillano, Eugeni López-Bonet, Begoña Martin-Castillo, Laura Castillo, Joan Brunet, Javier Cortes, Idoia Morilla, Isabel Alvarez, Jose Perez-Garcia
Přispěvatelé: 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, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2019
Předmět:
Oncology
medicine.medical_specialty
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES]
medicine.medical_treatment
Population
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
Mama -- Càncer -- Tractament
Therapeutics
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Càncer de mama
03 medical and health sciences
breast cancer
Breast cancer
0302 clinical medicine
Mama - Càncer
Trastuzumab
Internal medicine
medicine
Metformina
education
030304 developmental biology
neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES]
0303 health sciences
education.field_of_study
Chemotherapy
Taxane
Breast -- Cancer -- Treatment
business.industry
Communication
General Medicine
Terapèutica
medicine.disease
Metformin
Regimen
Tolerability
030220 oncology & carcinogenesis
residual disease
metformin
business
Ki67
medicine.drug
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Scientia
Recercat: Dipósit de la Recerca de Catalunya
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Journal of Clinical Medicine
Journal of Clinical Medicine (JCM), 2019, vol. 8, núm. 12, p. 2180
Articles publicats (IdIBGi)
DUGiDocs – Universitat de Girona
instname
Recercat. Dipósit de la Recerca de Catalunya
ISSN: 2077-0383
2016-8063
DOI: 10.3390/jcm8122180
Popis: Metformina; Ki67; Càncer de mama Metformina; Ki67; Cáncer de mama Metformin; Ki67; Breast cancer 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 (
Databáze: OpenAIRE
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