Author, as appears in the article.: Cuyas, Elisabet; Buxo, Maria; Ferri Iglesias, Maria Jose; Verdura, Sara; Pemas, Sonia; Dorca, Joan; Alvarez, Isabel; Martinez, Susana; Perez-Garcia, Jose Manuel; Batista-Lopez, Norberto; Rodriguez-Sanchez, Cesar A.; Amillano, Kepa; Dominguez, Severina; Luque, Maria; Morilla, Idoia; Stradella, Agostina; Vinas, Gemma; Cortes, Javier; Joven, Jorge; Brunet, Joan; Lopez-Bonet, Eugeni; Garcia, Margarita; Saidani, Samiha; Queralt Moles, Xavier; Martin-Castillo, Begona; Menendez, Javier A.;

Department: Medicina i Cirurgia

URV's Author/s: Joven Maried, Jorge

Keywords: Rs11212617 Pancreatic-cancer Neoadjuvancy Metformin Her2 Breast cancer Atm tumors therapy rs11212617 restriction resistant prevention neoadjuvancy models her2 chemotherapy breast cancer atm

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.

Thematic Areas: Saúde coletiva Oncology Medicina ii Medicina i Interdisciplinar Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cancer research Biotecnología

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 2234943X

Author's mail: jorge.joven@urv.cat

Author identifier: 0000-0003-2749-4541

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.frontiersin.org/articles/10.3389/fonc.2019.00193/full

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Frontiers In Oncology. 9 (MAR): 193-

APA: Cuyas, Elisabet; Buxo, Maria; Ferri Iglesias, Maria Jose; Verdura, Sara; Pemas, Sonia; Dorca, Joan; Alvarez, Isabel; Martinez, Susana; Perez-Garcia, J (2019). The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin. Frontiers In Oncology, 9(MAR), 193-. DOI: 10.3389/fonc.2019.00193

Article's DOI: 10.3389/fonc.2019.00193

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

Publication Type: Journal Publications