Effect of Benign Thyroid Disease on the Risk and Aggressiveness of Breast Cancer: An Updated Systematic Review and Meta-Analysis

Abstract BackgroundThe relationship between benign thyroid disease (BTD) and breast cancer (BC) has been discussed for a long time. However, the exact connection and underlying mechanism between them remained controversial. Our meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, and at the same time assessing whether benign thyroid disease exerts an influence on the aggressiveness of brea†st cancer.MethodA literature search was performed using PubMed, Web of Science, MEDLINE, and Embase databases for studies published from 1982 to August 2020. All data including odds ratio (OR) and its corresponding 95% confidence intervals (CI) were analyzed using STATA software, version 16.0. Publication bias and quality assessment of the included studies were conducted.ResultAfter strict literature search and selection, 18 articles were included in our meta-analysis. The result showed that autoimmune thyroiditis (OR 2.57, 95%CI 1.96–3.38), goiter (OR 2.13, 95%CI 1.19-3.79), and Graves’ disease (OR 4.17, 95%CI 1.08-16.05) were associated with increased risk of BC. Both hypothyroidism (OR 0.82, 95%CI 0.64-1.04) and hyperthyroidism (OR 1.07, 95%CI 0.93-1.24) had no correlations with the risk of breast cancer. Additionally, our pooled analysis showed no significant correlation was observed between benign thyroid disease and aggressiveness of breast cancer on the whole. However, a positive relationship was found between benign thyroid disease and aggressiveness of breast cancer in the Europe subgroup (HR:2.05, 95%CI 1.32-3.17).ConclusionAmong benign thyroid disease, autoimmune thyroiditis, goiter, and Graves’ disease were related to the increased risk of breast cancer. As a whole, benign thyroid disease was positively associated with the risk of breast cancer. Thus, special attention should be paid to these patients during treatment and follow-up. Additionally, benign thyroid disease increases the aggressiveness of breast cancer in the European population while no significant correlation was observed in other subgroups. Thus, more large-scale cohort studies are urgently needed soon to confirm the results. † Mingyue Han, Xue Zhao and Yao Wang should be considered shared first authors.