Statins and risk of breast cancer recurrence

Sakellakis, Minas; Akinosoglou, Karolina; Kostaki, Anastasia; Spyropoulou, Despina; Koutras, Angelos

doi:10.2147/bctt.s116694

Cited by 24 publications

(22 citation statements)

References 51 publications

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“…One major reason is lacking recurrence prevention drugs ( 29 , 30 ). According to retrospective studies, many drugs marketed for other diseases have shown an anti-tumor effect, which make them probably can be used for cancer recurrence prevention ( 31 – 33 ). Due to time-saving, lower cost, and streamlined approval processes, screening FDA-approved non-anti-tumor drugs for cancer prevention or recurrence prevention is attractive ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Xie

Zhang

et al. 2020

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.

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Section: Discussionmentioning

confidence: 99%

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Xie

Zhang

et al. 2020

Front. Oncol.

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“…For all statin users, the authors found a nonsignificant reduced risk of an SBCE. 16 Finally, regarding recurrence, in a retrospective study with the most extensive follow-up, Sakellakis et al 17 found that statin users had a longer mean relapse-free survival by ~6 years, and younger statin users (<56 years old) were observed to benefit the most by ~10 years as compared with other users (refer Table 1 for an overview of the association between statin use and risk of recurrence after multivariate analysis).…”

Section: Statins and Breast Cancer Recurrence Rates And Prognosismentioning

confidence: 99%

Effect of statins on breast cancer recurrence and mortality: a review

Wyhe¹,

Rahal²,

Woodward³

2017

BCTT

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Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are medications that have been used for decades to lower cholesterol and to prevent or treat cardiovascular diseases. Since their approval by the US Food and Drug Administration in the 1980s, other potential uses for statins have been speculated on and explored. Basic science and clinical research suggest that statins are also effective in the management of breast cancer. Specifically, in various breast cancer cell lines, statins increase apoptosis and radiosensitivity, inhibit proliferation and invasion, and decrease the metastatic dissemination of tumors. Clinical trials in breast cancer patients support these laboratory findings by demonstrating improved local control and a mortality benefit for statin users. A role for statins in the management of aggressive breast cancers with poor outcomes – namely, inflammatory breast cancer and triple-negative breast cancer – is particularly implicated. However, data exist showing that statins may actually promote invasive breast disease after long-term use and thus should be prescribed cautiously. Furthermore, a general consensus on the type of statin that should be administered, for how long, and when in relation to time of diagnosis is lacking. Given their low toxicity profile, affordability, and ease of use, consideration of statins as a therapy for breast cancer patients is imminent. In this review, we summarize current evidence regarding statins and clinical breast cancer outcomes, as well as discuss potential future studies that could shed light on this increasingly relevant topic.

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“…The characteristics of the included cohorts were shown in Table 1 . Eight of them were prospective cohort studies ( 12 , 14 , 16 – 18 , 25 , 26 , 28 ), while the other nine were retrospective ( 13 , 15 , 19 – 23 , 25 , 27 ). Women with breast cancer of different clinical stages were included.…”

Section: Resultsmentioning

confidence: 99%

“…Ten cohort studies ( 12 , 13 , 15 , 18 – 20 , 23 , 24 , 26 , 27 ) reported the association between statin use and recurrence of breast cancer. In the original manuscript from Li, the HR results for breast cancer recurrence were reported according to the time of statin use (<3, 3–5, and >5 years) ( 27 ).…”

Section: Resultsmentioning

confidence: 99%

Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies

Shi

Fei

et al. 2020

Front. Oncol.

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Background: Statin, a lipid-lowering drug, has been suggested to confer anticancer efficacy. However, previous studies evaluating the association between statin use and prognosis in breast cancer showed inconsistent results. A meta-analysis was performed to evaluate the association between statin use and clinical outcome in women with breast cancer. Methods: Cohort studies comparing recurrence or disease-specific mortality in women with breast cancer with and without using of statins were identified by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, incorporating the inter-study heterogeneity, was used to combine the results. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcomes Results: Seventeen cohort studies with 168,700 women with breast cancer were included. Pooled results showed that statin use was significantly associated with a lower risk of breast cancer recurrence (adjusted hazard ratio [HR] = 0.72, p < 0.001) and breast cancer mortality (HR = 0.80, p < 0.001). Subgroup analysis showed that timing of statin use, statin type, study design, sample size, or quality score did not significantly affect the outcomes. However, statin use was associated with more remarkably reduced breast cancer recurrence in studies with mean follow-up duration ≤ 5 years (HR = 0.55, p < 0.001) than that in studies of >5 years (HR = 0.83, p = 0.01). Conclusions: Statin use is associated with reduced recurrence and disease-specific mortality in women with breast cancer. These results should be validated in randomized controlled trials.

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Statins and risk of breast cancer recurrence

Cited by 24 publications

References 51 publications

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Effect of statins on breast cancer recurrence and mortality: a review

Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies

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