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A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk

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Abstract

Pre-clinical and epidemiologic studies provide rationale for evaluating lipophilic statins for breast cancer prevention. We conducted a single-arm, biomarker modulation trial of lovastatin among women with increased risk of breast cancer. Eligibility criteria included a deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53; lifetime breast cancer risk of ≥20 % as estimated by the Claus model; or personal history of estrogen receptor and progesterone receptor-negative breast cancer. Participants received 40 mg of lovastatin orally twice daily for 6 months. We evaluated the following biomarkers before and after lovastatin use: breast duct cytology (primary endpoint), serum lipids, C-reactive protein, insulin-like growth factor-1, IGF binding protein-3, lipid peroxidation, oxidative DNA damage, 3-hydroxy-3-methylglutaryl CoA reductase genotype, and mammographic density. Thirty women were enrolled, and 26 (86.7 %) completed the study. For the primary endpoint of changes in breast duct cytology sampled by random periareolar fine needle aspiration, most participants [57.7 %, 95 % confidence interval (CI) 38.9–74.5 %] showed no change after lovastatin; 19.2 % (CI 8.1–38.3 %) had a favorable change in cytology, 7.7 % (95 % CI 1.0–25.3 %) had an unfavorable change, and 15.4 % (95 % CI 5.5–34.2 %) had equivocal results due to acellular specimens, usually after lovastatin. No significant changes were observed in secondary biomarker endpoints. The study was generally well-tolerated: 4 (13.3 %) participants did not complete the study, and one (3.8 %) required a dose reduction. This trial was technically feasible, but demonstrated no significant biomarker modulation; contributing factors may include insufficient sample size, drug dose and/or duration. The results are inconclusive and do not exclude a favorable effect on breast cancer risk.

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Acknowledgments

Support for this study was provided by a 2005 American Society of Clinical Oncology Young Investigator Award to A.W.K., a 2005 Cancer Research and Prevention Foundation Post-Doctoral Fellowship Award to A.W.K. and J.M.F., an award from the Breast Cancer Research Foundation to J.M.F, and by the Jan Weimer Memorial Research Fund at Stanford University. The authors thank all study participants.

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The authors report no conflicts of interest.

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Authors and Affiliations

  1. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Shaveta Vinayak, Elizabeth Alli, Lisa McPherson, Adrian M. Fernandez, Vandana B. Sharma, Ashley Staton, Meredith A. Mills, Elizabeth A. Schackmann, Melinda L. Telli, Ani Kardashian, James M. Ford & Allison W. Kurian

  2. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Erich J. Schwartz & Kristin Jensen

  3. Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA

    Jafi Lipson

  4. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

    James M. Ford

  5. Department of Health Research and Policy, Stanford University School of Medicine, HRP Redwood Building, Room T254A, 150 Governor’s Lane, Stanford, CA, 94305-5405, USA

    Allison W. Kurian

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  1. Shaveta Vinayak
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  2. Erich J. Schwartz
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  15. Allison W. Kurian
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Correspondence to Allison W. Kurian.

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Vinayak, S., Schwartz, E.J., Jensen, K. et al. A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk. Breast Cancer Res Treat 142, 389–398 (2013). https://doi.org/10.1007/s10549-013-2739-z

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