|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 24, No 13 (May 1), 2006: pp. 2127 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.04.9882
A Call for Clinical Trials: Lipophilic Statins May Prove Effective in Treatment and Prevention of Particular Breast Cancer SubtypesUniversity of California San Francisco, San Francisco, CA To the Editor: The recent article by Bonovas et al1 in the Journal of Clinical Oncology found no protective effect of statins against breast cancer. However, epidemiologic studies on statins and breast cancer are limited by self-reporting and dose-duration effects. Typically, these studies contain inadequate data on the type of statin used; although there are two classes of statins, only lipophilic statins permeate the cell membrane to influence cell proliferation, survival, and motility.2 For example, in the article by Bonovas et al, four of the seven randomized clinical trials included in the analysis tested pravastatin, a lipophobic statin which past studies show to not affect cancer growth in vitro or in vivo.3 Statin randomized clinical trials to date are designed around cardiac and vascular end points, not cancer. Furthermore, data from two large retrospective studies presented at American Society of Clinical Oncology Annual Meetings were excluded from the meta-analyses, as they have not yet been published. Kochhar et al (n = 40,421) demonstrated a protective benefit of statins (relative risk, 0.49), increasing with longer duration of use.4 Mortimer et al (n = 68,071) found a significant reduction in breast cancers among women older than 50 years of age, conferred by statin use.5 The best way to demonstrate effect in humans is through randomized trials of lipophilic statins with a breast cancer-related end point. As statins are safe, health-promoting drugs, which have sustained over 30 years of drug development and extensive clinical scrutiny, there is little risk in testing them in the clinical setting. We are conducting a pilot trial of preoperative exposure to statins in an effort to better define which types of breast cancer may be most affected by statins, and which biomarkers are most likely to demonstrate that effect. This pilot perioperative biomarker trial is currently underway at four sites (Boston, MA, Chicago, IL, San Francisco, CA, and New York, NY). Data will hopefully inform future trials of statins in breast cancer. Our preclinical work demonstrates that estrogen receptor (ER) –negative breast cancer cell lines are more sensitive to growth inhibition by statins than ER-positive cell lines. In vivo, statin treatment significantly reduced tumor volume in an ER-negative strain of murine mammary carcinoma.3 These findings are consistent with a study we will present at the 2006 San Antonio Breast Cancer Symposium (n = 2,141). Breast cancer patients with more than 1 year of lipophilic statin use were less likely to develop ER-negative cancers. As such, it is likely that statins are more effective in particular tumor types. While the epidemiologic evidence supporting statin reduction of breast cancer risk is mixed, overwhelming preclinical data, in conjunction with a handful of case control studies, offer promise for statins' potential role as a cancer preventative. Lipophilic statins may prove more effective in preventing certain subgroups of ER-negative breast cancers (eg, basal type) versus the more common ER-positive types of breast cancer for which effective chemoprevention therapy already exists (eg, tamoxifen). These questions can only be answered by clinical trials. We hope that our pilot trial will provide sufficient evidence of effect to help launch such trials. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Bonovas S, Filioussi K, Tsavaris N, et al: Use of statins and breast cancer: A meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 23:8606-8612, 2005 2. Katz MS: Therapy insight: Potential of statins for cancer chemoprevention and therapy. Nat Clin Pract Oncol 2:82-89, 2005[CrossRef][Medline] 3. Esserman LJ, Campbell MJ, Shoemaker M, et al: Breast cancer inhibition by statins. J Clin Oncol 22:97s, 2004 (suppl; abstr 1003) 4. Kochhar R, Khurana V, Bejjanki H, et al: Statins to reduce breast cancer risk: A case control study in U.S. female veterans. J Clin Oncol 23:7s, 2005 (suppl; abstr 514) 5. Mortimer J, Axelrod R, Zimbro K: Effect of statins on breast cancer incidence: Findings from the Sentara Health Plan. Proc Am Soc Clin Oncol 22:93, 2003 (abstr 373) Related Reply
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
