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Review
. 2014 Sep;15(10):e461-8.
doi: 10.1016/S1470-2045(14)70119-6.

Statins and breast cancer prognosis: evidence and opportunities

Thomas P Ahern  1 , Timothy L Lash  2 , Per Damkier  3 , Peer M Christiansen  4 , Deirdre P Cronin-Fenton  5
Affiliations
Review

Statins and breast cancer prognosis: evidence and opportunities

Thomas P Ahern et al. Lancet Oncol. 2014 Sep.

Abstract

Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins--especially simvastatin--on breast cancer recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities--including candidate predictive biomarkers of statin safety and efficacy--and offer solutions to the key challenges involved in the enrolment, follow-up, and analysis of such a trial.

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Conflict of interest statement

CONFLICTS OF INTEREST

No author declared a conflict of interest.

Figures

FIGURE 1
FIGURE 1
Statins interrupt the enzymatic reduction of HMG-CoA to mevalonate. This prevents synthesis of cholesterol and two isoprenoids, farnesyl-PP and geranylgeranyl-PP, which post-translationally modify oncogenic proteins. Dashed arrows represent multi-step transitions.
FIGURE 2
FIGURE 2
Disposition of simvastatin. Simvastatin lactone (SVL) is absorbed and hydrolysed to simvastatin acid (SVA). SVA enters hepatocytes viaOATP1B1. Reactions catalysed by CYP3A4/5 yield oxidized compounds (SVOx), which are eliminated.
FIGURE 3
FIGURE 3
Published associations between statin use and breast cancer recurrence. Diamonds represent recurrence rate ratio point estimates; grey boxes are proportional to inverse-variance weights. Error lines represent 95% confidence intervals.
See this image and copyright information in PMC

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