Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

中文翻译：

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二甲双胍使用与手术切除乳腺癌生存之间关联的潜在内在亚型依赖性：一项韩国全国人口研究

目的

许多研究表明，二甲双胍治疗可以提高乳腺癌的存活率；然而，尚不清楚其影响是否与内在亚型或糖尿病状态相互作用。因此，我们进行了一项大型全国性研究，以评估手术切除的浸润性乳腺癌女性的这一情况。

方法

使用韩国国家健康保险理赔数据库确定 2007 年至 2016 年间新诊断的乳腺癌患者。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，乳腺癌亚型分为四组。

结果

总共包括 117,333 名患者（中位随访时间，90 个月）。2 型糖尿病 (T2DM) 显着影响总生存期（OS，7 年，89.7% 与 92.4%，p  < 0.001）。在 T2DM 患者中发现使用二甲双胍和胰岛素之间存在显着的相互作用（p  = 0.018）。因此，随后的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的 OS 显着增加（7 年 OS，88.3% 与 85.6%，p  < 0.001）。有趣的是，在激素治疗 (HT)+/HER2 靶向治疗 (Tx)- 组中观察到了显着效果（p  < 0.001），而在 HT-/HER2 Tx- 组中未观察到特定关联（p = 0.220）。

结论

二甲双胍给药可能与手术切除的乳腺癌患者死亡率降低有关，尤其是在 HT+/HER2 Tx- 组中。研究二甲双胍作为乳腺癌联合用药的临床试验应通过根治性切除、内在亚型、T2DM 的存在和胰岛素的使用对患者进行分层。