Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Boramae-ro 5 gil, 20, Dongjak-gu, Seoul, Korea.
Department of Radiation Oncology, Chungnam National University College of Medicine, Munhwa-ro 282, Jungku, Daejeon, 35015, Korea.
Int J Clin Oncol. 2021 Nov;26(11):2004-2016. doi: 10.1007/s10147-021-02005-8. Epub 2021 Aug 10.
Numerous studies have suggested that metformin treatment can increase breast cancer survival; however, it is unclear whether its effects interact with intrinsic subtype or diabetic status. Therefore, we conducted a large nationwide study to assess this in women with surgically resected invasive breast cancer.
Patients with newly diagnosed breast cancer between 2007 and 2016 were identified using the national health insurance claims database of South Korea. Metformin or other drug exposures was defined as medication for ≥ 90 days. Breast cancer subtypes were classified into four groups based on hormonal therapy and anti-HER2 treatments.
A total of 117,333 patients were included (median follow-up duration, 90 months). Type 2 diabetes mellitus (T2DM) affected significantly overall survival (OS, 7 years, 89.7% vs. 92.4%, p < 0.001). A significant interaction was found between the use of metformin and insulin in patients with T2DM (p = 0.018). Thus, the subsequent analysis was limited to these patients and propensity score matching was performed. We found significantly increased OS in patients treated with metformin (7-year OS, 88.3% vs. 85.6%, p < 0.001). Interestingly, a significant effect was observed in the hormonal therapy (HT)+/HER2-targeted therapy (Tx)- group (p < 0.001), whereas no specific association was observed in the HT-/HER2 Tx- group (p = 0.220).
Metformin administration may be associated with reduced mortality in patients with surgically resected breast cancer, particularly in the HT+/HER2 Tx- group. Clinical trials investigating metformin as a combination agent in breast cancer should stratify patients by curative resection, intrinsic subtype, the presence of T2DM, and the use of insulin.
大量研究表明二甲双胍治疗可提高乳腺癌的生存率，但尚不清楚其疗效是否与内在亚型或糖尿病状态有关。因此，我们进行了一项大规模的全国性研究，以评估二甲双胍对接受手术切除的浸润性乳腺癌女性的影响。
使用韩国国家健康保险索赔数据库，确定 2007 年至 2016 年间新诊断为乳腺癌的患者。二甲双胍或其他药物暴露定义为用药时间≥90 天。根据激素治疗和抗 HER2 治疗，将乳腺癌亚型分为四组。
共纳入 117333 例患者（中位随访时间 90 个月）。2 型糖尿病（T2DM）显著影响总生存期（OS，7 年，89.7% vs. 92.4%，p<0.001）。在 T2DM 患者中，二甲双胍和胰岛素的使用存在显著的交互作用（p=0.018）。因此，后续分析仅限于这些患者，并进行了倾向评分匹配。我们发现，接受二甲双胍治疗的患者 OS 显著延长（7 年 OS，88.3% vs. 85.6%，p<0.001）。有趣的是，在激素治疗（HT）+/HER2 靶向治疗（Tx）-组中观察到显著的效果（p<0.001），而在 HT-/HER2 Tx-组中未观察到特定的相关性（p=0.220）。
二甲双胍的应用可能与接受手术切除的乳腺癌患者的死亡率降低相关，尤其是在 HT+/HER2 Tx-组中。在乳腺癌中，作为联合治疗药物，二甲双胍的临床试验应根据根治性切除术、内在亚型、T2DM 的存在以及胰岛素的使用情况对患者进行分层。
