Is Gestational Diabetes Mellitus a Risk Factor of Maternal Breast Cancer? A Systematic Review of the Literature.

Julien Simon,Sonia Bechraoui-Quantin,Patrick Arveux,Karine Goueslard,Catherine Quantin

doi:10.3390/biomedicines9091174

Abstract

The association between gestational diabetes mellitus (GDM) and breast cancer (BC) risk is complex. We aimed to examine this association in a systematic review of the literature. This review was done using the PubMed/Medline and Web of Science databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle–Ottawa Scale was used for the assessment of bias and quality of studies. Only English-language articles published before 1 June 2021, were included. Fourteen studies were included in this systematic review. Among them, eight did not find statistically significant results. Three studies showed a statistically significant increased risk of BC after GDM, and they explained this potential increased risk by hyperinsulinemia, hyperglycemia, and low-grade inflammation. However, three studies showed a statistically significant decreased risk of BC after GDM, suggesting a possible protective effect of hormonal changes induced by GDM during pregnancy. These controversial results should be interpreted with caution due to both quantitative and qualitative methodological shortcomings. Further investigations are thus needed in order to gain a better understanding of the associations between GDM and BC, and their underlying mechanisms.

Highlights

IntroductionWomen with diabetes have a 15–20% increased risk of Breast cancer (BC) compared to women without diabetes [2,3,4,5,6,7,8]
Breast cancer (BC) is the most common cancer, accounting for about one fourth of all cancer cases in women in Europe and worldwide [1].Women with diabetes have a 15–20% increased risk of BC compared to women without diabetes [2,3,4,5,6,7,8]
We included all types of clinical studies reporting the association between gestational diabetes mellitus (GDM) and BC with statistics available for adjusted odds ratio (OR) or relative risk (RR) and 95% confidence intervals (CI)

Summary

Introduction

Women with diabetes have a 15–20% increased risk of BC compared to women without diabetes [2,3,4,5,6,7,8]. Underlying mechanisms include the effects of hyperinsulinemia on sex steroid availability [9,10] and IGF-1 production [11,12]. Hormone-independent mechanisms, including chronic inflammation with elevated levels of pro-inflammatory cytokines, infiltration of fat deposits by pro-inflammatory macrophages, and associated oxidative stress, have been suggested [13]. Women with gestational diabetes mellitus (GDM) have an increased risk of diabetes, even in the first few years following delivery [14,15,16]. GDM shares underlying mechanisms with type 2 diabetes, including hyperglycemia due to pancreatic β-cell dysfunction coupled with insulin resistance and hyperinsulinemia.

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