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

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.