Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer.

Yeo-Jin Choi,Sooyoung Shin,Keunhyeong Bak,Yoon Yeo,Yongwon Choi

doi:10.3390/ph14090925

Abstract

Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors. This retrospective cohort study included female patients with early-stage breast cancer, treated with or without SERMs, between 2008 and 2020 in a tertiary care hospital in Korea. Four propensity score-matched comparison pairs were designed: SERM use versus non-use, long-term use (≥1500 days) versus non-use, tamoxifen use versus non-use, and toremifene use versus non-use; then, logistic regression analysis was performed for risk analysis. SERMs in general were not associated with an elevated risk of diabetes; however, when used for ≥1500 days, SERMs—especially toremifene—substantially increased diabetes risk in breast cancer patients (OR 1.63, p = 0.048). Meanwhile, long-term SERM treatment was effective at preventing metastatic cancer (OR 0.20, p < 0.001) and death (OR 0.13, p < 0.001). SERM treatment, albeit generally safe and effective, may increase diabetes risk with its long-term use in women with breast cancer. Further studies are required to verify the association between toremifene treatment and incident diabetes.

Highlights

A pathophysiological link between diabetes and cancer has been suggested in several studies; diabetic patients are predisposed to cancer and vice versa when compared with their healthy counterparts, mediated by shared risk factors between the two disease states, metabolic alterations, and complications over disease progression, along with adverse effects from prolonged exposure to pharmacologic therapies [1,2,3,4,5,6]
Given that toremifene is primarily used in postmenopausal women as opposed to tamoxifen whose use is recommended in both preand post-menopausal women with estrogen receptor (ER)/progesterone receptor (PR) positive breast cancer [11], toremifene users tend to be older than tamoxifen users, which may have played a role in differential outcomes per Selective estrogen receptor modulators (SERMs) agent
To the best of our knowledge, this is the first study that incorporated both tamoxifen and toremifene—two SERM agents approved to treat breast cancer—in risk analyses stratified by patient factors, high-risk comedication patterns, and treatment duration to evaluate their effects on incident diabetes in female breast cancer survivors

Summary

Introduction

A pathophysiological link between diabetes and cancer has been suggested in several studies; diabetic patients are predisposed to cancer and vice versa when compared with their healthy counterparts, mediated by shared risk factors between the two disease states, metabolic alterations, and complications over disease progression, along with adverse effects from prolonged exposure to pharmacologic therapies [1,2,3,4,5,6]. Given that the survival rates are projected to steadily grow, prevention of long-term complications and adverse effects from pharmacological therapies is of crucial importance in enhancing morbidity and mortality of breast cancer survivors. As these patients are likely to receive anticancer treatments repeatedly to prevent cancer progression and metastatic spread, more research is required to have a better insight into the prognostic role of these therapies with respect to metabolic complications, such as incident diabetes risks.

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