Statin drugs to reduce breast cancer recurrence and mortality

Colin H Beckwitt, Adam Brufsky, Zoltán N Oltvai, Alan Wells, Colin H Beckwitt, Adam Brufsky, Zoltán N Oltvai, Alan Wells

Abstract

Epidemiologic studies have, variably, shown the concomitant use of statin drugs to be beneficial to cancer outcomes. Statin drugs have been FDA approved for three decades for the treatment of high cholesterol and atherosclerotic coronary artery disease and are widely used. This has engendered studies as to their influence on concomitant diseases, including cancers. In this context, statin use has been correlated, variably, with a decrease in deaths from breast cancer. However, there is no extant model for this effect, and the extent of efficacy is open to question.The overarching goal of this article is to communicate to the reader of the potential of statins to reduce breast cancer progression and mortality. This is the use as a secondary prevention measure, and not as a therapy to directly counter active cancer. First, salient aspects of statin pharmacology, as relates to cardiovascular disease, will be discussed. Second, the basic and clinical research studies that investigate statin usage in breast cancer will be presented. Additionally, statin effects in other cancer types will be included for context. Finally, proposals for future basic and clinical research studies to determine the role of statins in breast cancer management will be presented.

Keywords: Breast cancer; Lipophilicity; Metastasis; Prenylation; Secondary prevention; Statins.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
The cholesterol biosynthesis pathway. Statins block HMG-CoA reductase (HMGCR, shown in blue) to shut down the cholesterol biosynthetic pathway. In addition to cholesterol, other downstream mediators are affected, such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP)
Fig. 2
Fig. 2
Proposed model for statin action in breast cancer. a The breast cancer metastatic cascade. Statins (red) block emergence of dormant breast cancer cells at the site of micrometastasis to prevent their emergence to form clinically evident metastases. b Statins (red) block HMG-CoA reductase (HMGCR) to decrease the number of prenylation groups (Pr), such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, available for prenylating small G proteins, such as Ras (shown), Rac, and RhoA. Decreased prenylation reduces membrane tethering of these G proteins, which reduces downstream proliferative and pro-EMT signaling. Drawing made using images from Servier Medical Art [101]

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