Breast Cancer Research and Treatment

, Volume 142, Issue 2, pp 389–398

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

  • Shaveta Vinayak
  • Erich J. Schwartz
  • Kristin Jensen
  • Jafi Lipson
  • 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
Clinical Trial


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.


Breast cancer Cancer prevention Cancer risk reduction BRCA1/2 Lovastatin Clinical trial Biomarkers Random periareolar fine needle aspiration 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shaveta Vinayak
    • 1
  • Erich J. Schwartz
    • 2
  • Kristin Jensen
    • 2
  • Jafi Lipson
    • 3
  • Elizabeth Alli
    • 1
  • Lisa McPherson
    • 1
  • Adrian M. Fernandez
    • 1
  • Vandana B. Sharma
    • 1
  • Ashley Staton
    • 1
  • Meredith A. Mills
    • 1
  • Elizabeth A. Schackmann
    • 1
  • Melinda L. Telli
    • 1
  • Ani Kardashian
    • 1
  • James M. Ford
    • 1
    • 4
  • Allison W. Kurian
    • 1
    • 5
  1. 1.Department of MedicineStanford University School of MedicineStanfordUSA
  2. 2.Department of PathologyStanford University School of MedicineStanfordUSA
  3. 3.Department of RadiologyStanford University School of MedicineStanfordUSA
  4. 4.Department of GeneticsStanford University School of MedicineStanfordUSA
  5. 5.Department of Health Research and PolicyStanford University School of MedicineStanfordUSA

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