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http://hdl.handle.net/2445/167997
Title: | Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer |
Author: | López Bonet, Eugeni Buxó, Maria Cuyàs, Elisabet Pernas, Sònia Dorca, Joan Álvarez López, Isabel Martinez, Susana Pérez García, José Manuel Batista López, Norberto Rodríguez Sánchez, César A. Amillano, Kepa Domínguez, Severina Luque, Maria Morilla, Idoia Stradella, Agostina Viñas, Gemma Cortés, Javier Oliveras, Glòria Melendez, Cristina Castillo, Laura Verdura, Sara Brunet, Joan Joven, Jorge Garcia, Margarita Saidani, Samiha Martin Castillo, Begoña Menendez, Javier A. |
Keywords: | Càncer de mama Terapèutica Breast cancer Therapeutics |
Issue Date: | 1-Dec-2019 |
Publisher: | MDPI |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/jcm8122180 |
It is part of: | Journal of Clinical Medicine, 2019, vol. 8, num. 12 |
URI: | http://hdl.handle.net/2445/167997 |
Related resource: | https://doi.org/10.3390/jcm8122180 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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Lopez-BonetE.pdf | 18.69 MB | Adobe PDF | View/Open |
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