Glucocorticoids and breast cancer risk

Glucocorticoids are essential endogenous steroid hormones secreted in response to stress, and treatment with synthetic forms is widespread for numerous inflammatory conditions including asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, and arthritis [1]. Emerging evidence suggests that glucocorticoids can exert both anti- and pro-inflammatory effects, modulated through suppressing or augmenting immune response [1]. Given these divergent biologic properties, glucocorticoids could theoretically reduce breast cancer risk via anti-inflammatory effects or could increase breast cancer risk and progression by inducing insulin resistance and promoting immunosuppression [2]. Yet, despite biological plausibility, epidemiologic studies of glucocorticoid use and breast cancer are limited.

New data
As such, the recent prospective cohort study by Cairat et al. [3] is an important contribution to the literature as an investigation into the potential role of glucocorticoids in breast cancer etiology. In this study, authors evaluated associations between glucocorticoid use and breast cancer risk among over 65,000 postmenopausal French women in the E3N cohort. Using linkage to outpatient health expenditures, authors observed that receipt of at least two reimbursements of systemic glucocorticoids was associated with a reduced risk of invasive breast cancer, which appeared to follow a dose-response trend with increasing number of reimbursements. The observed associations did not differ substantially by type of glucocorticoid, or by timing or duration of use. However, inverse associations were significant only among women older than 60 years at first use. In stratified analyses, the inverse associations were restricted to estrogen receptor (ER)-positive tumors, and stage I and II disease. Interestingly, authors also observed positive associations between glucocorticoids and risk of in situ breast cancer and stage III/IV breast cancer, although confidence intervals for these measures of association were wide given smaller numbers of cases. In sensitivity analysis, only recurrent users (not occasional users) were at higher risk of in situ or stage III or IV disease and only recurrent users were at lower risk of stage I or II breast cancer. The authors conclude that the association between systemic glucocorticoid use and breast cancer risk may differ by tumor subtypes and stage of disease.

Unlike prior studies, Cairat et al. were able assess whether the associations of glucocorticoids and breast cancer differed according to hormone receptor status, histological subtype, tumor grade, and stage at diagnosis. This is particularly important given the various pharmacological properties of glucocorticoids and evidence for cross-talk between estrogen receptors and glucocorticoid receptors in mammary epithelial cells [4], which suggests that glucocorticoids could differentially impact breast cancer subtypes. An additional strength of this study was the inclusion of comprehensive information on potential confounders including body mass index, alcohol consumption, family history of breast cancer, and use of nonsteroidal anti-inflammatory medication; factors which were not considered in prior population registry-based studies in Denmark [5, 6] where no associations between receipt of glucocorticoid prescription and breast cancer risk were observed.

This study is informative in teasing apart heterogeneity in glucocorticoid-breast cancer