The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin

• Published in: Frontiers in oncology Vol. 9; p. 193
• Main Authors: Cuyàs, Elisabet, Buxó, Maria, Ferri Iglesias, Maria José, Verdura, Sara, Pernas, Sonia, Dorca, Joan, Álvarez, Isabel, Martínez, Susana, Pérez-Garcia, Jose Manuel, Batista-López, Norberto, Rodríguez-Sánchez, César A, Amillano, Kepa, Domínguez, Severina, Luque, Maria, Morilla, Idoia, Stradella, Agostina, Viñas, Gemma, Cortés, Javier, Joven, Jorge, Brunet, Joan, López-Bonet, Eugeni, Garcia, Margarita, Saidani, Samiha, Queralt Moles, Xavier, Martin-Castillo, Begoña, Menendez, Javier A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28-03-2019
• Subjects: ATM; breast cancer; HER2; metformin; neoadjuvancy; Oncology; rs11212617; neoadjuvancy; breast cancer; metformin; ATM; rs11212617; HER2
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.00193

The minor allele (
) of the single-nucleotide polymorphism (SNP)
, located near the
(
) 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).
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
genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction.
Logistic regression analyses revealed a significant relationship between the
genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR]
= 10.33, 95% confidence interval [CI]: 1.29-82.89,
= 0.028). In the metformin-containing arm, patients bearing the
allele had a significantly higher probability of pCR (OR
= 7.94, 95%CI: 1.60-39.42,
= 0.011). Conversely, no association was found between
and clinical response in the reference arm (OR
= 0.77, 95%CI: 0.20-2.92,
= 0.700). After controlling for tumor size and hormone receptor status, the
allele remained a significant predictor of pCR solely in the metformin-containing arm.
If reproducible, the
allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in BC patients.
EU Clinical Trials Register, EudraCT number 2011-000490-30. Registered 28 February 2011, https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000490-30/ES.