1. The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin
- Author
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Elisabet Cuyàs, Maria Buxó, Maria José Ferri Iglesias, Sara Verdura, Sonia Pernas, Joan Dorca, Isabel Álvarez, Susana Martínez, Jose Manuel Pérez-Garcia, Norberto Batista-López, César A. Rodríguez-Sánchez, Kepa Amillano, Severina Domínguez, Maria Luque, Idoia Morilla, Agostina Stradella, Gemma Viñas, Javier Cortés, Jorge Joven, Joan Brunet, Eugeni López-Bonet, Margarita Garcia, Samiha Saidani, Xavier Queralt Moles, Begoña Martin-Castillo, and Javier A. Menendez
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Population ,Mama -- Càncer -- Tractament ,Type 2 diabetes ,lcsh:RC254-282 ,Càncer de mama ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Clinical trials ,Trastuzumab ,Internal medicine ,HER2 ,medicine ,neoadjuvancy ,education ,Metformina ,education.field_of_study ,Breast -- Cancer -- Treatment ,business.industry ,rs11212617 ,Biochemical markers ,Odds ratio ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Metformin ,Clinical trial ,Minor allele frequency ,030104 developmental biology ,030220 oncology & carcinogenesis ,ATM ,Marcadors bioquímics ,business ,metformin ,medicine.drug ,Assaigs clínics - Abstract
The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). Methods: DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery. SNP rs11212617 genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction. Results: Logistic regression analyses revealed a significant relationship between the rs11212617 genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR]genotype×arm = 10.33, 95% confidence interval [CI]: 1.29–82.89, p = 0.028). In the metformin-containing arm, patients bearing the rs11212617 C allele had a significantly higher probability of pCR (ORA/C,C/C = 7.94, 95%CI: 1.60–39.42, p = 0.011). Conversely, no association was found between rs11212617 and clinical response in the reference arm (ORA/C,C/C = 0.77, 95%CI: 0.20–2.92, p = 0.700). After controlling for tumor size and hormone receptor status, the rs11212617 C allele remained a significant predictor of pCR solely in the metformin-containing arm. Conclusions: If reproducible, the rs11212617 C allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in 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 BM-C). Work in the Menendez laboratory is supported by the Ministerio de Ciencia e Innovación [Grant SAF2016-80639-P, Plan Nacional de l+D+I, founded by the European Regional Development Fund (EU FEDER), Spain] and by an unrestricted research grant from the Fundació Oncolliga Girona (Lliga catalana d’ajuda al malalt de càncer, Girona)
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- 2019