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Journal of Clinical Oncology, Vol 24, No 13 (May 1), 2006: pp. 2127-a-2128 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.06.1515
In ReplyDepartments of Pharmacology and Pathophysiology, School of Medicine, University of Athens, Athens, Greece We appreciate the comments by Kumar, Campbell, Benz, and Esserman in regard to our article1 examining the association between statin use and breast cancer risk. However, they raise a number of issues, which we would like to discuss. By design, the seven randomized clinical trials (RCTs) included in our meta-analysis are not limited by self-reporting of drug exposure. Similarly, six of nine incorporated observational studies used existing computerized databases that provide detailed information on drug prescription. This information is equally good for cases and controls irrespective of the event of interest, since it was recorded prospectively. To investigate the hypothesis that lipophilic statins may have a different chemopreventive effect than lipophobic, we have further restricted the meta-analysis of RCTs to the three trials of lipophilic statins.2-4 The association of statin use with breast cancer risk was once again not statistically significant (random effects model: relative risk, 0.97; 95% CI, 0.60 to 1.55; I2, 25%). Kumar et al correctly notice that RCTs to date are designed around cardiovascular end points. However, we should not overlook that site-specific cancer incidence, among other secondary end points, is also well studied and reported. Indeed, each separate trial lacks the statistical power to come to definite conclusions regarding the association between statin use and cancer risk. Therefore, performing a meta-analysis permits synthesis of data, which may lead to resolution of uncertainty and disagreement. Regarding the findings of the retrospective study of Mortimer et al5 presented at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003: the data reported in this abstract suggests that young women (< 50 years) who are treated with statins may be at increased risk for the development of breast cancer (P < .001), while no association exists between statin use and breast cancer risk among women older than 50 years of age.5 Kumar et al claim that the question of whether statin use affects breast cancer risk remains unanswered. Beyond any doubt, the synthesis of the existing epidemiologic data does not support an association between statin use and breast cancer risk. However, a beneficial or even a harmful effect of certain statins on particular breast cancer subtypes cannot be excluded. In addition, Kumar et al suggest that the best way to demonstrate effect in humans is through randomized trials of lipophilic statins with a breast cancer–related end point, assuming that there is little risk in testing them in the clinical setting. However, one should not overlook that we do not know the effect of statins in normal people, those without high cholesterol or high triglycerides. Conducting such a trial brings the dangers that come with giving drugs to otherwise healthy people. We would like to note that next to those preclinical studies offering promise for statins' potential role as a cancer preventative, there are also studies providing evidence for a carcinogenic effect of statins in rodents.6 Given the cancer latency, it is important to continue monitoring statins' profiles for extended follow-up periods (perhaps through national registries) to identify whether any effects might emerge in the longer term. 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. Strandberg TE, Pyorala K, Cook TJ, et al: Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival study (4S). Lancet 364:771-777, 2004[CrossRef][Medline] 3. Downs JR, Clearfield M, Weis S, et al: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279:1615-1622, 1998 4. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 360:7-22, 2002[CrossRef][Medline] 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) 6. Newman TB, Hulley SB: Carcinogenicity of lipid-lowering drugs. JAMA 275:55-60, 1996[Abstract] Related Correspondence
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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