Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor–Positive Early Breast Cancer

Estrogen receptor-positive early breast cancer is common and has a relatively good prognosis. It shares risk factors with cardiovascular disease, and cardiovascular disease is an important competing cause of mortality. Adjuvant endocrine therapy with aromatase inhibitors (requiring concomitant ovarian suppression in premenopausal women) or selective estrogen receptor modulators (usually tamoxifen) exert oncologic benefits by respectively inhibiting estradiol synthesis or breast estrogen receptor signaling. Aromatase inhibitors cause systemic estradiol depletion. Tamoxifen has mixed agonistic/antagonistic effects in a tissue-dependent fashion. Given that estrogens modulate cardiometabolic risk, a review of the effects of endocrine therapy on cardiometabolic outcomes is pertinent. The current, but limited, evidence suggests that tamoxifen treatment, although associated with increases in body fat, hepatic steatosis, serum triglycerides, and diabetes risk, modestly reduces low-density lipoprotein cholesterol and lipoprotein(a) and may have favorable effects on markers of subclinical atherosclerosis. Tamoxifen is associated with either no effect on, or a reduction in, cardiovascular events, and it is associated with an increase in venous thromboembolic events. Aromatase inhibitors, although fewer studies are available and often confounded by comparison with tamoxifen, have not been consistently associated with adverse changes in cardiometabolic risk factors or increases in cardiovascular events. Further clinical trials designed to evaluate cardiometabolic outcomes are needed to more accurately determine the effects of endocrine therapy on cardiovascular risks, to inform individualized decisions regarding choice and duration of endocrine therapy, and to implement evidence-based strategies to mitigate cardiometabolic risks. In the meantime, although breast cancer-specific evidence for benefit of lifestyle measures is available and recommended routinely, proactive monitoring and treatment of cardiovascular risk factors should follow general population recommendations.