Harms of Screening Mammography
Mammography screening may be effective in reducing breast cancer mortality in certain populations, but it can pose harm to women who participate. The limitations are best described as false-positives (related to the specificity of the test), overdiagnosis (true-positives that will not become clinically significant), false-negatives (related to the sensitivity of the test), discomfort associated with the test, radiation risk and anxiety.
|Age, y||No. of Breast Cancer Deaths Averted With Mammography Screening Over Next 15 yb||No. (95% CI) With ≥1 False-Positive Result During the 10 yc||No. (95% CI) With ≥1 False Positive Resulting in a Biopsy During the 10 yc||No. of Breast Cancers or DCIS Diagnosed During the 10 y That Would Never Become Clinically Important (Overdiagnosis)d|
|No. = number; CI = confidence interval; DCIS = ductal carcinoma in situ.|
|aAdapted from Pace and Keating.|
|bNumber of deaths averted are from Welch and Passow. The lower bound represents breast cancer mortality reduction if the breast cancer mortality relative risk were 0.95 (based on minimal benefit from the Canadian trials [3,4]), and the upper bound represents the breast cancer mortality reduction if the relative risk were 0.64 (based on the Swedish 2-County Trial ).|
|cFalse-positive and biopsy estimates and 95% confidence intervals are 10-year cumulative risks reported in Hubbard et al.  and Braithwaite et al.|
|dOverdiagnosed cases are calculated by Welch and Passow. The lower bound represents overdiagnosis based on results from the Malmö trial, whereas the upper bound represents the estimate from Bleyer and Welch.|
|eThe lower-bound estimate for overdiagnosis reported by Welch and Passow  came from the Malmö study. The study did not enroll women younger than 50 years.|
|40||1–16||6,130 (5,940–6,310)||700 (610–780)||?–104e|
|50||3–32||6,130 (5,800–6,470)||940 (740–1,150)||30–137|
|60||5–49||4,970 (4,780–5,150)||980 (840–1,130)||64–194|
False-Positives Leading to Possible Additional Interventions
The specificity of mammography (refer to the Breast Cancer Screening Concepts section of this summary for more information) affects the number of additional interventions due to false-positive results. Even though breast cancer is the most common noncutaneous cancer in women, fewer than 5 per 1,000 women actually have the disease when they are screened. Therefore, even with a specificity of 90%, most abnormal mammograms are false-positives. Women with abnormal screening mammograms undergo additional mammographic imaging to magnify the area of concern, ultrasound, magnetic resonance imaging, and tissue sampling (by fine-needle aspiration, core biopsy, or excisional biopsy).
A study of breast cancer screening in 2,400 women enrolled in a health maintenance organization found that over a 10-year period, 88 cancers were diagnosed, 58 of which were identified by mammography. During that period, one-third of the women had an abnormal mammogram result that required additional testing, including 539 additional mammograms, 186 ultrasound examinations, and 188 biopsies. The cumulative biopsy rate (the rate of true-positives) due to mammographic findings was approximately 1 in 4 (23.6%). The positive predictive value (PPV) of an abnormal screening mammogram in this population was 6.3% for women aged 40 to 49 years, 6.6% for women aged 50 to 59 years, and 7.8% for women aged 60 to 69 years.  A subsequent analysis and modeling of data from the same cohort of women, all of whom were continuously enrolled in the Harvard Pilgrim Health Care plan from July 1983 through June 1995, estimated that the risk of having at least one false-positive mammogram was 7.4% (95% confidence interval [CI], 6.4%–8.5%) at the first mammogram, 26.0% (95% CI, 24.0%–28.2%) by the fifth mammogram, and 43.1% (95% CI, 36.6%–53.6%) by the ninth mammogram. Cumulative risk of at least one false-positive by the ninth mammogram varied from 5% to 100%, depending on four patient variables (younger age, higher number of previous breast biopsies, family history of breast cancer, and current estrogen use) and three radiologic variables (longer time between screenings, failure to compare the current and previous mammograms, and the individual radiologist’s tendency to interpret mammograms as abnormal). Overall, the biggest risk factor for having a false-positive mammogram was the individual radiologist’s tendency to read mammograms as abnormal.
A prospective cohort study of community-based screening found that a greater proportion of women undergoing annual screening had at least one false-positive screen after 10 years than did women undergoing biennial screening, regardless of breast density. For women with scattered fibroglandular densities, the difference was 68.9% (annual) versus 46.3% (biennial) for women in their 40s. For women aged 50 to 74 years, the difference for this density group was 49.8% (annual) versus 30.7% (biennial).
By reviewing Medicare claims following mammographic screening in 23,172 women older than 65 years, one study  found that, per 1,000 women, 85 had follow-up testing, 23 had biopsies, and 7 had cancer. Thus, the PPV for an abnormal mammogram was 8%. For women older than 70 years, the PPV was 14%.
An audit of mammograms performed in 1998 at a single institution revealed that 14.7% of examinations resulted in a recommendation for additional testing (Breast Imaging Reporting and Data System category 0), 1.8% resulted in a recommendation for biopsy (categories 4 and 5), and 5.7% resulted in a recommendation for short-term interval mammography (category 3). Cancer was diagnosed in 0.5% of the cases referred for additional testing. 
As shown in Table 3, the estimated number of women out of 10,000 who undergo annual screening mammography over a 10-year period with at least one false-positive result is 6,130 for women aged 40 to 50 years and 4,970 for women aged 60 years. The number of women with a false-positive resulting in a biopsy is estimated to range from 700 to 980, depending on age.
Overdiagnosed disease is a neoplasm that would never become clinically apparent without screening before a patient’s death. The prevalence of cancer in women who died of noncancer causes is surprisingly high. In an overview of seven autopsy studies, the median prevalence of occult invasive breast cancer was 1.3% (range, 0%–1.8%) and of ductal carcinoma in situ was 8.9% (range, 0%–14.7%).[16,17] A “perfect” screening test would identify approximately 10% of “normal” women as having breast cancer, even though most of those cancers would probably not result in illness or death. Treatment of these cancers would constitute overtreatment.
Currently, cancers that will cause illness and/or death cannot be confidently distinguished from those that will remain occult, so all cancers are treated.
To determine the number of screen-detected cancers that are overdiagnosed, one can compare breast cancer incidence over time in a screened population with that of an unscreened population.
Population-based studies could demonstrate the extent of overdiagnosis if the screened and nonscreened populations were the same except for screening. Unfortunately, the populations may differ in time, geography, culture, and the use of postmenopausal hormone therapy. Investigators also differ in their calculation of overdiagnosis as they adjust for characteristics such as lead-time bias.[18,19] As a consequence, the magnitude of overdiagnosis due to mammographic screening is controversial, with estimates ranging from 0% to 54%.[8,18-20]
Several observational population-based comparisons consider breast cancer incidence before and after adoption of screening.[21-25] If there were no overdiagnosis—and other aspects of screening were unchanged—there would be a rise in incidence followed by a decrease to below the prescreening level, and the cumulative incidence would be similar. Such results have not been observed. Breast cancer incidence rates increase at the initiation of screening without a compensatory drop in later years. One study in 11 rural Swedish counties showed a persistent increase in breast cancer incidence following the advent of screening. A population-based study showed increases in invasive breast cancer incidence of 54% in Norway and 45% in Sweden in women aged 50 to 69 years, following the introduction of nationwide screening programs. No corresponding decline in incidence in women older than 69 years was ever seen. Similar findings suggestive of overdiagnosis have been reported from the United Kingdom  and the United States.[24,25]
Estimates of the extent of overdiagnosis noted in the Canadian National Breast Screening Study, a randomized clinical trial, have been reported. At the end of the five screening rounds, an excess of 142 invasive breast cancer cases was diagnosed in the mammography arm, compared with the control arm. At 15 years, the excess number of cancer cases in the mammography arm versus the control arm was 106; this represents an overdiagnosis rate of 22% for the 484 screen-detected invasive cancers.
Table 3 shows the estimated number of women with breast cancers or ductal carcinoma in situ diagnosed during a 10-year period of screening 10,000 women that would never become clinically important (overdiagnosis). There was no overdiagnosis in the Health Insurance Plan study, which used old-technology mammography and clinical breast examination. Overdiagnosis has become more prominent in the era of improved-technology mammography. However, the benefits of newer-technology mammography over older-technology mammography in regard to reduced mortality have not been demonstrated.
False-Negatives Leading to Possible False Sense of Security
The sensitivity of mammography (refer to the Breast Cancer Screening Concepts section of this summary for more information) ranges from 70% to 90%, depending on a woman’s age and the density of her breasts, which is affected by her genetic predisposition, hormone status, and diet. Assuming an average sensitivity of 80%, mammograms will miss approximately 20% of the breast cancers that are present at the time of screening (false-negatives). Many of these missed cancers are high risk, with adverse biologic characteristics (refer to the Interval cancers section in the Breast Cancer Screening Concepts section of this summary for more information ). If a "normal" mammogram dissuades or postpones a woman or her doctor from evaluating breast symptoms, she may suffer adverse consequences. Thus, a negative mammogram should never prevent work-up of breast symptoms.
Compression of the breast is important during a mammogram to reduce motion artifact and improve image quality. Positioning of the woman is important. One study that evaluated how often pain and discomfort are felt during mammography reported that 90% of women undergoing mammography had discomfort, and 12% rated the sensation as intense or intolerable.
The major predictors of radiation risk are young age at exposure and dose. For women older than 40 years, the benefits of annual mammograms probably outweigh the potential risk, but certain subpopulations of women may have an inherited susceptibility to ionizing radiation damage.[30,31] In the United States, the mean glandular dose for screening mammography is 1 to 2 mSv per view or 2 mSv to 4 mSv per standard two-view exam.[32,33] By comparison, a single chest computed tomography (CT) scan delivers 7 mSv and an abdominal CT scan delivers 12 to 20 mSv. The whole-body environmental radiation dose is approximately 3 mSv per year. Thus, it may be estimated that up to one breast cancer may be induced per 1,000 women aged 40 to 80 years undergoing annual mammograms.
Because large numbers of women have false-positive tests, the issue of psychological distress—which may be provoked by the additional testing—has been studied. A telephone survey of 308 women performed 3 months after screening mammography revealed that about one-fourth of the 68 women with a “suspicious” result were still experiencing worry that affected their mood or functioning, even though subsequent testing had ruled out a cancer diagnosis. Several studies,[35-37] however, show that the anxiety following evaluation of a false-positive test leads to increased participation in future screening examinations.
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- Welch HG, Passow HJ: Quantifying the benefits and harms of screening mammography. JAMA Intern Med 174 (3): 448-54, 2014. [PUBMED Abstract]
- Miller AB, To T, Baines CJ, et al.: The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med 137 (5 Part 1): 305-12, 2002. [PUBMED Abstract]
- Miller AB, To T, Baines CJ, et al.: Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst 92 (18): 1490-9, 2000. [PUBMED Abstract]
- Tabár L, Vitak B, Chen TH, et al.: Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 260 (3): 658-63, 2011. [PUBMED Abstract]
- Hubbard RA, Kerlikowske K, Flowers CI, et al.: Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med 155 (8): 481-92, 2011. [PUBMED Abstract]
- Braithwaite D, Zhu W, Hubbard RA, et al.: Screening outcomes in older US women undergoing multiple mammograms in community practice: does interval, age, or comorbidity score affect tumor characteristics or false positive rates? J Natl Cancer Inst 105 (5): 334-41, 2013. [PUBMED Abstract]
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