To the Editor: I was troubled by the lack of a cost–benefitanalysis in the article by Fletcher and Elmore on the effectivenessof mammography for screening for breast cancer (April 24 issue).1In fairness, their recommendations are more fiscally conservativethan those of the U.S. Preventive Services Task Force. Still,their omission of any discussion of relative costs and benefitsgives the implicit message that cost does not matter.
William A. Hensel, M.D. Moses Cone Health System Greensboro, NC 27401 bill.hensel{at}mosescone.com
References
Fletcher SW, Elmore JG. Mammographic screening for breast cancer. N Engl J Med 2003;348:1672-1680. [Free Full Text]
To the Editor: The article by Fletcher and Elmore on mammographicscreening is potentially misleading because it lumps "recalls"together with false positive mammograms (Figure 1 of their article).A false positive mammogram refers to an interpretation of ascreening mammogram as abnormal in a case in which there isno accompanying diagnosis of cancer.1 A recall occurs when ascreening mammogram demonstrates an area of potential concernnecessitating additional mammographic views for clarification.An interpretation is not rendered until these additional viewsare obtained. A recall is therefore distinct from a false positivemammogram.
This point is more than one of simple semantics. If the distinctionbetween recalls and false positive interpretations is blurred,the negative effect of mammography is amplified. Such an analysiscreates a subtle bias against mammography, which could be mitigatedby careful adherence to these definitions.
Michael J. Fishbein, M.D. Falmouth Hospital Falmouth, MA 02540 mjf{at}massmed.org
References
Sickles EA, Ominsky SH, Sollitto RA, Galvin HB, Monticciolo DL. Medical audit of a rapid-throughput mammography screening practice: methodology and results of 27,114 examinations. Radiology 1990;175:323-327. [Free Full Text]
To the Editor: The tone of the article by Fletcher and Elmoresuggests that screening women in their 40s is still of questionablevalue. However, the rate of death due to breast cancer, as apercentage of the rate of death from any cause, is highest amongwomen in their 40s. A reduction in mortality of 20 percent amongwomen in their 40s is a low estimate. The Gothenberg BreastCancer Screening Trial,1 the Malmö Mammographic ScreeningProgram,2 and the Swedish trials3 showed statistically significantreductions in mortality of 44 percent, 35 percent, and 29 percent,respectively, among women younger than 50 years of age. Furthermore,because of noncompliance and contamination, the trials underestimatethe benefit. Women need to be provided with all the data inorder to make informed decisions. The concerns raised by Gøtzscheand Olsen were either unwarranted or of no consequence,4 andthe trial data remain valid.
Daniel B. Kopans, M.D. Harvard Medical School Boston, MA 02115
References
Bjurstam N, Björneld L, Duffy SW, et al. The Gothenberg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women ages 39–49. In: National Institutes of Health consensus conference on breast cancer screening for women ages 40–49. Journal of the National Cancer Institute monographs. No. 22. Bethesda, Md.: National Cancer Institute, 1997:53-5.
Andersson I, Janzon L. Reduced breast cancer mortality in women under 50: update from the Malmö Mammographic Screening Program. In: National Institutes of Health consensus conference on breast cancer screening for women ages 40–49. Journal of the National Cancer Institute monographs. No. 22. Bethesda, Md.: National Cancer Institute, 1997:63-7.
Hendrick RE, Smith RA, Rutledge JH III, Smart CR. Benefit of screening mammography in women ages 40–49: a new meta-analysis of randomized controlled trials. In: National Institutes of Health consensus conference on breast cancer screening for women ages 40–49. Journal of the National Cancer Institute monographs. No. 22. Bethesda, Md.: National Cancer Institute, 1997:87-92.
Kopans DB. The most recent breast cancer screening controversy about whether mammographic screening benefits women at any age: nonsense and nonscience. AJR Am J Roentgenol 2003;180:21-26. [Free Full Text]
To the Editor: Figure 2 in the article by Fletcher and Elmoremisleads the reader by exaggerating the number of lives savedby mammography by a factor of 5 to 10. First, the authors assumea 30 percent reduction in mortality among women 50 to 69 yearsof age. The latest meta-analysis estimates that the reductionis 16 percent.1 Second, the authors apply this 30 percent reductionin relative risk to the rate of death due to breast cancer calculatedon the basis of a screened population rather than a controlpopulation, thus compounding the error. They estimate that fourlives are saved by screening 1000 women 50 to 60 years of agefor 10 years and that six lives are saved by similar screeningamong women 60 to 70 years of age. In reality, the number neededto screen is 1224 to save 1 life over a 14-year period1 (approximately1713, over a 10-year period); in other words, 5.8 lives willbe saved per 10,000 women screened, not 4 or 6 per 1000 screened— almost a case of the missing zero. Among women youngerthan 50 years of age, the number needed to screen is approximately2508 — that is, over a 10-year period, 4 lives will besaved per 10,000 women screened, not 20 per 10,000, as estimatedby the authors.
Jayant S. Vaidya, M.B., B.S., Ph.D. Michael Baum, M.D. University College London London W1W 7EJ, United Kingdom j.vaidya{at}ucl.ac.uk
References
Humphrey LL, Helfand M, Chan BKS, Woolf SH. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:347-360. [Free Full Text]
To the Editor: Fletcher and Elmore's account of the issues isnot balanced. They describe a number of criticisms of our workthat have been raised and — conversely — contendthat all the criticisms of the mammography trials we raisedhave been answered, apart from those of one trial (in Edinburgh,Scotland) that was excluded from our meta-analysis.
First, the criticisms Fletcher and Elmore mention concern ourfirst article in the Lancet, which were answered in our CochraneReview and in our second Lancet article.1 Second, the most importantcriticisms we raised against the trials remain unanswered2,3:the biased misclassification of the cause of death, discrepanciesin numbers in the analyses of the Swedish trials, and differentialexclusions from analysis of women with breast cancer beforerandomization. For example, Fletcher and Elmore indicate thatthere was no problem with exclusions in the New York trial,but the trial's lead investigator admitted that even in 1985,more than 20 years after the study started, the investigatorswere unaware of some previous cases of breast cancer in controls,who should have been excluded.4
Peter C. Gøtzsche, M.D. Nordic Cochrane Centre 2100 Copenhagen, Denmark pcg{at}cochrane.dk
References
Olsen O, Gøtzsche PC. Cochrane Review on screening for breast cancer with mammography. Lancet 2001;358:1340-1342. [CrossRef][Web of Science][Medline]
Gøtzsche PC. Screening for breast cancer with mammography. Lancet 2001;358:2167-2168. [Web of Science][Medline]
Shapiro S. Discussion II. In: Selection, follow-up, and analysis in prospective studies: a workshop. National Cancer Institute monograph 67. Bethesda, Md.: National Cancer Institute, May 1985:75-9. (NIH publication no. 85-2713.)
The authors reply: We strongly agree with Dr. Hensel regardingthe importance of cost effectiveness. However, as we point outin our article, information about cost effectiveness is especiallyimportant for policymakers and payers when they are making decisionsabout the allocation of finite resources. The key issues forclinical practice are the underlying risk of the condition beingscreened for, the effectiveness of screening in the preventionof major untoward outcomes such as death, and the hazards associatedwith the screening procedure, such as false positive results.
Dr. Fishbein's concern about differentiating between recallsand false positive mammograms is understandable. The recallrate (which we defined as the percentage of mammograms thatresult in recommendations for further testing) includes bothfalse positive and true positive mammograms, but because mostpositive mammograms are false positives, lowering the recallrate would most likely reduce the risk of false positive mammograms;this is important, because many studies have shown that falsepositive mammograms make women anxious.1 Mammographers havea difficult task: they must not miss cancers, but they mustalso not recall too many women.
Dr. Kopans is concerned that the 20 percent reduction in therate of death due to breast cancer that we used to calculatethe number of women in their 40s whose lives would be savedby regular mammographic screening is too low, and Drs. Vaidyaand Baum think our estimates are too high. Estimates differmainly according to which trials are included in a given analysis.Whatever the estimate, Figure 2 of our article makes it possibleto translate the relative effect into absolute numbers. Forexample, we estimated that 2 of 1000 women who regularly underwentmammography during their 40s might owe their lives to mammography.If mortality due to breast cancer is reduced by 40 percent,the number would be about four.
In addition, Vaidya and Baum are concerned that we missed azero in our calculations. They are mistaken, since the numbersin the figure are based on 10,000 mammograms. Because mammographyis recommended repeatedly, we chose to demonstrate the effectof 10,000 mammograms in 1000 women tested annually for 10 years,rather than that of 10,000 mammograms in 10,000 women testedonce each. We also included many other effects of a programof regular screening mammography.
We made a list of Dr. Gøtzsche's concerns about the randomizedtrials, along with responses we found, and presented them ina table in a supplementary appendix on the Journal's Web site(available with the full text of our article at http://www.nejm.org).Interested readers can review the list there.
Finally, we wish to point out an error in our article. The statement(beginning on the last line of page 1674) that "obtaining mammogramsduring the luteal phase of the menstrual cycle may decreasemammographic density" should have read "obtaining mammogramsduring the luteal phase of the menstrual cycle may decreasemammographic sensitivity."
Suzanne W. Fletcher, M.D. Harvard Medical School Boston, MA 02115
Joann G. Elmore, M.D., M.P.H. University of Washington Seattle,WA 98104
References
Vainio H, Bianchini F. Breast cancer screening. Lyons, France: IARC Press, 2002.
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