The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Sahebkar, Amirhossein; Şerban, Corina; Penson, Peter E.; Gurban, Camelia; Ursoniu, Sorin; Tóth, Peter P.; Jones, Steven R.; Lippi, Giuseppe; Kotani, Kazuhiko; Kostner, Karam; Rizzo, Manfredi; Rysz, Jacek; Banach, Maciej

doi:10.1007/s40265-017-0767-4

Cited by 34 publications

(23 citation statements)

References 66 publications

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“…These changes were sustained in a subgroup of 62 women followed for 5 years [60]. At 5 years, a modest decrease in lipoprotein(a) [Lp(a)] was reported [60] and subsequently confirmed by a small meta-analysis of five RCTs with 215 participants (standardized mean difference, −0.41; 95% CI, −0.68 to −0.14; P = 0.003) [61]. Similar effects of tamoxifen on lipid parameters have been reported in smaller placebo-controlled studies in women with early breast cancer [62].…”

Section: Effects Of Endocrine Therapy On Cardiometabolic Outcomesmentioning

confidence: 93%

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

Cheung

Ramchand

Yeo

et al. 2019

Journal of the Endocrine Society

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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.

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Section: Effects Of Endocrine Therapy On Cardiometabolic Outcomesmentioning

confidence: 93%

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

Cheung

Ramchand

Yeo

et al. 2019

Journal of the Endocrine Society

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“…However, whilst Lp(a) elevation is associated with cardiovascular disease it is still unclear if there is a benefit in therapeutically targeting its reduction specifically. Although no specific therapy for lowering Lp(a) is as yet approved, the body of evidence supports the reducing effects by lipoprotein apheresis 54 , proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 55 , estrogen mimics and selective estrogen receptor modulators 56–58 , nicotinic acid 59 and some nutraceuticals 60–63 . Moreover, selective apo(a) antisense therapy has shown promising lowering effects in patients with elevated Lp(a) in phase II trials 64 .…”

Section: Discussionmentioning

confidence: 99%

Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials

Sahebkar

Simental‐Mendía

Pirro

et al. 2018

Sci Rep

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The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of ezetimibe on plasma lipoprotein(a) concentrations. Only randomized placebo-controlled trials investigating the impact of ezetimibe treatment on cholesterol lowering that include lipoprotein(a) measurement were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to February 26th, 2018). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on lipoprotein concentrations. This meta-analysis of data from 10 randomized placebo-controlled clinical trials (15 treatment arms) involving a total of 5188 (3020 ezetimibe and 2168 control) subjects showed that ezetimibe therapy had no effect on altering plasma Lp(a) concentrations (WMD: −2.59%, 95% CI: −8.26, 3.08, p = 0.370; I2 = 88.71%, p(Q) < 0.001). In the subgroup analysis, no significant alteration in plasma Lp(a) levels was observed either in trials assessing the impact of monotherapy with ezetimibe versus placebo (WMD: −4.64%, 95% CI: −11.53, 2.25, p = 0.187; I2 = 65.38%, p(Q) = 0.005) or in trials evaluating the impact of adding ezetimibe to a statin versus statin therapy alone (WMD: −1.04%, 95% CI: −6.34, 4.26, p = 0.700; I2 = 58.51%, p(Q) = 0.025). The results of this meta-analysis suggest that ezetimibe treatment either alone or in combination with a statin does not affect plasma lipoprotein(a) levels.

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“…We are cautious to extend the results to other populations. Secondly, endocrine therapy such as tamoxifen, toremifene and aromatase inhibitors is essential for breast cancer patients, 29 – 31 which can also lead to dyslipidemia. We did not include patients using these drugs due to the limited sample size, which makes it impossible to carefully distinguish their effect on blood lipids from that of (neo)adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

<p>Dynamic Changes of Blood Lipids in Breast Cancer Patients After (Neo)adjuvant Chemotherapy: A Retrospective Observational Study</p>

Xu¹,

Dong²,

Long³

et al. 2020

IJGM

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Background: Previous studies indicated that the (neo)adjuvant chemotherapy for breast cancer can cause significant dyslipidemia in patients, but how long this abnormality can persist is unclear so far. The purpose of this study is to investigate whether (neo)adjuvant chemotherapy has a long-term effect on blood lipids in breast cancer patients. Methods: A total of 159 newly diagnosed female breast cancer patients receiving the (neo) adjuvant chemotherapy subsequently and 159 female healthy controls were enrolled into the observational study. All participants' blood lipid profiles which included TC, TG, HDL-C, and LDL-C before and at the end of the 1st and 12th month after chemotherapy were retrieved from the electronic medical record system. The blood lipid profiles and the percentage of dyslipidemia before and after chemotherapy in breast cancer patients and controls were compared. Results: Compared with the baseline before chemotherapy, TC, LDL-C, and TG increased significantly at the end of the 1st month after chemotherapy, but only the abnormal increase in TG (2.98±0.71 mmol/L vs 2.82±0.63 mmol/L, P<0.05) and LDL-C (1.82±0.42 mmol/L vs 1.59±0.42 mmol/L, P<0.05) continued until the 12th month after chemotherapy. Levels of HDL-C in breast cancer patients and all the blood lipid parameters in controls remained stable during the observation period. The percentage of dyslipidemia in breast cancer patients rose from 41.5% at baseline to 54.1% at the 12th month after chemotherapy. Subgroup analysis demonstrated that the increase in dyslipidemia percentage was more pronounced in patients with low body mass index and aged over 50 years. Conclusion: The (neo)adjuvant chemotherapy used for treating breast cancers can cause significant abnormalities in blood lipid profiles, and the abnormal increase in LDL-C and TG can last at least 12 months after chemotherapy, which indicates long-term management of blood lipid is necessary for those patients.

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The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Cited by 34 publications

References 66 publications

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

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

Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials

<p>Dynamic Changes of Blood Lipids in Breast Cancer Patients After (Neo)adjuvant Chemotherapy: A Retrospective Observational Study</p>

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