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
Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.
Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
Front Oncol. 2019 Mar 28;9:193. doi: 10.3389/fonc.2019.00193. eCollection 2019.
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.
位于（）基因附近的单核苷酸多态性（SNP）的次要等位基因（）与2型糖尿病患者使用二甲双胍治疗成功的可能性增加有关。我们在此研究了同一SNP是否能预测早期乳腺癌（BC）女性患者对新辅助二甲双胍的临床反应。DNA取自METTEN研究意向性治疗人群中的79例患者，该研究为一项2期临床试验，HER2阳性BC患者被随机分为两组，一组在术前接受二甲双胍联合蒽环类/紫杉类化疗及曲妥珠单抗治疗，另一组接受不含二甲双胍的等效方案治疗。使用定量聚合酶链反应的等位基因鉴别法评估SNP基因分型。逻辑回归分析显示，（）基因型与治疗组患者实现病理完全缓解（pCR）的能力之间存在显著关联（比值比[OR]=10.33，95%置信区间[CI]：1.29 - 82.89，=0.028）。在含二甲双胍的治疗组中，携带（）等位基因的患者pCR概率显著更高（OR = 7.94，95%CI：1.60 - 39.42，=0.011）。相反，在对照组中未发现（）与临床反应之间存在关联（OR = 0.77，95%CI：0.20 - 2.92，=0.700）。在控制肿瘤大小和激素受体状态后，（）等位基因仍然仅是含二甲双胍治疗组中pCR的显著预测指标。如果结果可重复，（）等位基因可能值得作为预测性临床生物标志物来考虑，以指导BC患者二甲双胍的个体化使用。欧盟临床试验注册中心，EudraCT编号2011 - 000490 - 30。于2011年2月28日注册，https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000490-30/ES。
