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

Abstract

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.

Breast Cancer Survivors Undergoing Endocrine Therapy Have a Worrying Risk Factor Profile for Cardiovascular Diseases

“…In addition to previous treatments, the current therapy with AIs may lead to increased cardiovascular risk [ 12 ]. As mentioned, this may occur due to a reduction in the levels of estrogen, a hormone associated with cardiovascular protection [ 13 ]. It is worth mentioning that, despite this, such treatments are extremely important for women diagnosed with BC [ 8 ] and should not be discouraged.…”

“…Among the drugs used in this treatment, aromatase inhibitors (AIs) have high efficacy in women in the postmenopausal stage [ 10 , 11 ], however, they are associated with increased risk of vascular disease, myocardial infarction and angina [ 12 ]. One possible explanation is that the drug reduces estrogen levels, and these hormones are related to cardiovascular protection [ 13 ]. A prospective study has shown that 80% of women with prescriptions for this therapy have a predicted risk of CVDs in ten years equal to or higher than the risk of recurrence of BC [ 14 ].…”

Management of Early Menopause/Premature Ovarian Insufficiency in Women with or at High Risk of Breast Cancer

“…However, the available evidence suggests that neither tamoxifen nor aromatase inhibitors are associated with increased cardiovascular events. 55 More detailed evidence is needed in this cohort to better guide the management of cardiovascular risk in women after breast cancer.…”

Endothelial Glycocalyx-Mediated Intercellular Interactions: Mechanisms and Implications for Atherosclerosis and Cancer Metastasis

“…64 Recent reports by Suzuki et al and others suggest that patients with atherosclerotic plaques could be at a higher risk for developing cancer. 19,32,103 Other reports indicate that long-term cardiovascular risk attenuates cancer survival rate and efficacy of early cancer therapy, particularly with respect to breast cancer, which has been the cancer of focus in our research laboratory. 36,53 Furthermore, it is known that cardiovascular disease contributes to a majority of the deaths amongst breast cancer patients.…”