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Title: The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin
Author: Cuyàs, Elisabet
Buxó, Maria
Ferri Iglesias, Maria José
Verdura, Sara
Pemas, Sonia
Dorca, Joan
Álvarez, Isabel
Martínez, Susana
Pérez García, José Manuel
Batista López, Norberto
Rodríguez Sánchez, César A.
Amillano, Kepa
Domínguez, Severina
Luque, María
Morilla, Idoia
Stradella, Agostina
Vinas, Gemma
Cortés, Javier
Joven, Jorge
Brunet, Joan
López Bonet, Eugeni
García, Margarita
Saidani, Samiha
Queralt Moles, Xavier
Martin Castillo, Begoña
Menendez, Javier A.
Keywords: Càncer de mama
Marcadors bioquímics
Assaigs clínics
Breast cancer
Biochemical markers
Clinical trials
Issue Date: 1-Jan-2019
Publisher: Frontiers Media Sa
Abstract: Background: 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](genotypexarm) = 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.
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It is part of: Frontiers In Oncology, 2019-01-01, Vol. 9 num. 193
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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