A mortality reduction of 1 per 1,000 may not sound significant, but considering that there are millions of women in the United States who are eligible for screening, even a small reduction in mortality rate translates to thousands of deaths avoided.
—Carol H. Lee, MD, FACR
Despite evidence from a number of prospective, randomized controlled trials showing that screening mammography reduces breast cancer mortality, screening mammography has been the subject of continual debate, controversy, and conflicting guidelines. Recently, the Swiss Medical Board, tasked with reviewing existing data, took the arguments against screening to their extreme, recommending that no new screening mammography programs be introduced and that existing programs be subject to a time limit. This recommendation, explained in a New England Journal of Medicine article1 that is reviewed in this issue of The ASCO Post, is a stunning example of how vastly different conclusions can be reached from the same data.
The authors cited three main points as the basis of the board’s recommendation: (1) the use of old data to support benefits of mammography, (2) the lack of evidence that benefits of screening outweigh harms, and (3) misperception of the magnitude of screening benefit among screening candidates.
The authors note that evidence for the benefit of screening is based on old data, with the first trials conducted more than 50 years ago. In the face of improved treatment, they claim, modern screening may not perform as well. This statement is based on conjecture rather than on concrete data and does not take into consideration the fact that imaging technology has improved substantially since the first trials were conducted. It is just as valid to postulate that screening may perform better now than in the trials because marked improvements in the technical quality of mammography may result in greater ability to detect early cancer.
The authors cite the recent update of the Canadian National Breast Screening study that did not show a reduction in breast cancer mortality2 but fail to note that seven other randomized controlled trials did indeed show mortality reduction.3-9 They also fail to note that in the United States, breast cancer mortality remained unchanged for 50 years but began to decline approximately 5 to 7 years after screening mammography became widespread and is now more than 30% lower than in the prescreening era.
Certainly, some of that benefit is due to improved treatment—but treatment of early-stage breast cancer is successful more often than that of late-stage disease, and mammography remains the best way to detect early breast cancer. In addition, it is interesting to note that breast cancer mortality in males, who are not screened but who receive treatment similar to that for females, has not changed during the same period that breast cancer mortality among women has substantially decreased.10
Benefits vs Harms
Second, the authors emphasize how “nonobvious” it was in their review of data that the benefits of screening outweigh the harms. They note that existing data indicate a mortality reduction of 20%, or roughly 1 breast cancer death averted for every 1,000 women screened. They also observe, however, that there was no decrease in all-cause mortality and that the benefit is outweighed by “harms,” consisting of false-positive readings and overdiagnosis.
However, none of the randomized trials of screening mammography was designed or powered to evaluate all-cause mortality. With regard to false-positive findings, a recall from screening is resolved in the majority of cases by simply performing a few additional mammographic views and/or ultrasound. In a small proportion of cases, a biopsy is necessary to exclude malignancy, but this is usually achieved by minimally invasive core needle biopsy.
These so-called harms are hardly equal to the possible benefit of having a small, treatable breast cancer detected through screening. Indeed, a survey conducted in the United States found that 63% of women thought that 500 false-positive readings was reasonable to save one life and that 37% would tolerate 10,000 false-positive examinations.11 A recent study showed that the anxiety associated with an abnormal screening mammogram is short-lived and does not result in significant psychological harm or a decreased willingness to participate in future screenings.12
Overdiagnosis vs Overtreatment
With regard to “overdiagnosis,” the term is a misnomer. Cancers that are detected are histologically malignant and therefore not, strictly speaking, overdiagnosed. Because of the inability to differentiate those cancers that would never progress to become life-threatening from those that would, all cancers are treated as if they are potentially lethal. Therefore, the more correct term in this setting is “overtreatment.”
The degree to which overtreatment occurs is unclear, with estimates varying widely from < 1% to > 50%. In its analysis of the existing literature, the U.S. Preventive Services Task Force put the estimate at roughly 10%.13 The answer to overdiagnosis or overtreatment should be to develop cellular or molecular means of separating potentially lethal cancers from innocent ones. It is not reasonable to stop screening in order to avoid overtreating a minority of cases while sacrificing the opportunity to detect and appropriately treat the majority.
Finally, the authors conveyed their uneasiness with the fact that the public seems to have a misperception as to the benefits of screening mammography, with the majority grossly overestimating its ability to reduce breast cancer mortality. This does not seem to be a reason to stop screening, but rather constitutes a call for health-care providers to improve education of their patients and encourage shared wdecision-making about whether or not to screen.
The recommendation of the Swiss Medical Board that screening mammography no longer be offered to Swiss women is disturbing. A mortality reduction of 1 per 1,000 may not sound significant, but considering that there are millions of women in the United States who are eligible for screening, even a small reduction in mortality rate translates to thousands of deaths avoided—and it has been repeatedly demonstrated both by prospective trials and by actual clinical experience that mammography does indeed save lives. ■
Dr. Lee is Attending Radiologist, Memorial Sloan Kettering Cancer Center, Professor of Radiology, Weill Cornell Medical College, New York.
Disclosure: Dr. Lee reported no potential conflicts of interest.
1. Biller-Andorno N, Jüni P: Abolishing mammography screening programs? A view from the Swiss Medical Board. N Engl J Med 370:1965-1967, 2014.
2. Miller AB, Wall C, Baines CJ, et al: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 348:366-376, 2014.
3. Shapiro S, Venet W, Strax P, et al: 10- to 14-year effect of screening on breast cancer mortality. J Natl Cancer Inst 69:349-355, 1982.
4. Nystrom L, Andersson I, Bjurstam N, et al: Long-term effects of mammography screening: Updated overview of the Swedish randomised trials. Lancet 359:909-919, 2002.
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6. Tabar L, Fagerberg G, Chen HH, et al: Efficacy of breast cancer screening by age: New results from the Swedish Two-County Trial. Cancer 75:2507-2517, 1995.
7. Frisell J, Lidbrink E: The Stockholm Mammographic Screening Trial: Risks and benefits in age group 40-49 years. J Natl Cancer Inst Monogr (22):49-51, 1997.
8. Bjurstam N, Bjorneld L, Duffy SW, et al: The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49. J Natl Cancer Inst Monogr (22):53-55, 1997.
9. Alexander FE, Anderson TJ, Brown HK, et al: 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 353:1903-1908, 1999.
10. Centers for Disease Control and Prevention: Cancer Statistics by Cancer Type. Available at www.cdc.gov/cancer/dcpc/data/types.htm. Accessed June 5, 2014.
11. Schwartz LM, Woloshin S, Sox HC, et al: US women’s attitudes to false positive mammography results and detection of carcinoma in situ: A cross sectional study. BMJ 320:1635-140, 2000.
12. Tosteson ANA, Fryback DG, Hammond CS, et al: Consequences of false-positive screening mammograms. JAMA Intern Med 174:954-961, 2014.
13. Nelson HD, Tyne K, Naik A, et al: U.S. Preventive Services Task Force. Screening for breast cancer: An update from the U.S. Preventive Services Task Force. Ann Intern Med 151:727-737, 2009.
In a New England Journal of Medicine “Perspective” article, Nikola Biller-Andorno, MD, PhD, of the University of Zurich and Harvard Medical School, and Peter Jüni, MD, of the University of Bern, provide the rationale for a recent report by the Swiss Medical Board advocating the phasing out of...