Dataset Information

Aromatase inhibitor use is a risk factor of carotid plaque presence in endocrine-responsive breast cancer patients.

ABSTRACT:

Background/aims

The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs.

Methods

A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed.

Results

The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation.

Conclusion

There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.

SUBMITTER: Seo DH

PROVIDER: S-EPMC6506747 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Aromatase inhibitor use is a risk factor of carotid plaque presence in endocrine-responsive breast cancer patients.

Seo Da Hea DH Cho Yongin Y Lee Sujin S Park Seho S Kim Seung-Il SI Park Byeong Woo BW Rhee Yumie Y

The Korean journal of internal medicine 20170825 3

<h4>Background/aims</h4>The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive bre ...[more]

PMID: 28838227

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Project description:Although aromatase inhibitors (AIs; for example, letrozole) are highly effective in treating estrogen receptor positive (ER+) breast cancer, a significant percentage of patients either do not respond to AIs or become resistant to them. Previous studies suggest that acquired resistance to AIs involves a switch from dependence on ER signaling to dependence on growth factor-mediated pathways, such as human epidermal growth factor receptor-2 (HER2). However, the role of HER2, and the identity of other relevant factors that may be used as biomarkers or therapeutic targets remain unknown. This study investigated the potential role of transcription factor hypoxia inducible factor 1 (HIF-1) in acquired AI resistance, and its regulation by HER2.In vitro studies using AI (letrozole or exemestane)-resistant and AI-sensitive cells were conducted to investigate the regulation and role of HIF-1 in AI resistance. Western blot and RT-PCR analyses were conducted to compare protein and mRNA expression, respectively, of ER?, HER2, and HIF-1? (inducible HIF-1 subunit) in AI-resistant versus AI-sensitive cells. Similar expression analyses were also done, along with chromatin immunoprecipitation (ChIP), to identify previously known HIF-1 target genes, such as breast cancer resistance protein (BCRP), that may also play a role in AI resistance. Letrozole-resistant cells were treated with inhibitors to HER2, kinase pathways, and ER? to elucidate the regulation of HIF-1 and BCRP. Lastly, cells were treated with inhibitors or inducers of HIF-1? to determine its importance.Basal HIF-1? protein and BCRP mRNA and protein are higher in AI-resistant and HER2-transfected cells than in AI-sensitive, HER2- parental cells under nonhypoxic conditions. HIF-1? expression in AI-resistant cells is likely regulated by HER2 activated-phosphatidylinositide-3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, as its expression was inhibited by HER2 inhibitors and kinase pathway inhibitors. Inhibition or upregulation of HIF-1? affects breast cancer cell expression of BCRP; AI responsiveness; and expression of cancer stem cell characteristics, partially through BCRP.One of the mechanisms of AI resistance may be through regulation of nonhypoxic HIF-1 target genes, such as BCRP, implicated in chemoresistance. Thus, HIF-1 should be explored further for its potential as a biomarker of and therapeutic target.

Dataset Information

Aromatase inhibitor use is a risk factor of carotid plaque presence in endocrine-responsive breast cancer patients.

Background/aims

Methods

Results

Conclusion

Publications

Aromatase inhibitor use is a risk factor of carotid plaque presence in endocrine-responsive breast cancer patients.

Similar Datasets

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