Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark.
Breast Cancer Res. 2024 Nov 4;26(1):150. doi: 10.1186/s13058-024-01908-4.
Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.
We conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.
Of 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83-1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.
This large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.
妊娠糖尿病（GDM）是一种常见的妊娠并发症，其特征为胰岛素抵抗。有研究表明，胰岛素抵抗与乳腺癌之间存在关联，而乳腺癌是女性最常见的癌症。因此，患有既往 GDM 的女性可能有更高的乳腺癌发病风险，但现有证据存在矛盾。本研究探讨了 GDM 与乳腺癌发病的相关性，包括癌症诊断时的年龄。此外，我们还研究了妊娠期间胰岛素抵抗严重程度和随后发生糖尿病对乳腺癌风险的潜在影响。
我们进行了一项全国性、基于登记的队列研究，纳入了 1997 年至 2018 年期间在丹麦分娩的所有女性。我们根据 ICD-10 代码定义 GDM 和乳腺癌。绝经前和绝经后乳腺癌分别定义为结局年龄<50 岁和≥50 岁。妊娠期间胰岛素抵抗严重程度的替代指标基于胰岛素治疗；产后存在 ICD-10 代码和/或抗糖尿病药物定义为后续糖尿病。统计学分析包括 Cox 回归、逻辑回归和 t 检验。
在 708121 名女性中，3.4%患有 GDM。中位随访时间为 11.9 年（范围 0-21.9）。既往有 GDM 的女性与无 GDM 的女性的总体乳腺癌风险相当（调整后的危险比 0.96 [95%CI 0.83-1.12]）。绝经前和绝经后乳腺癌风险也没有差异；然而，既往有 GDM 的女性的乳腺癌诊断年龄更小（42.6 岁 vs. 43.5 岁，p 值<0.01）。无论 GDM 病史如何，全因死亡率相似。妊娠期间胰岛素抵抗严重程度和随后发生糖尿病并未影响乳腺癌风险。
这项大型基于人群的队列研究显示，在中位随访近 12 年后，与无既往 GDM 的女性相比，既往有 GDM 的女性发生乳腺癌的风险没有更高。这在绝经状态方面均成立。乳腺癌风险不受妊娠期间胰岛素抵抗严重程度和随后发生糖尿病的影响。无论 GDM 病史如何，都应优先关注乳腺癌的预防、早期发现和治疗。
