Additional Interventions
False Sense of Security
Radiation Exposure
Anxiety
Overdiagnosis

Mammography screening may be effective in reducing breast cancer mortality in certain populations. As with any medical intervention, it has limitations, which can pose potential harm to women who participate. These limitations are best described as false-negatives (related to the sensitivity of the test), false-positives (related to the specificity), overdiagnosis (true positives that will not become clinically significant), and radiation risk.

The specificity of mammography (refer to the Mammography section) affects the number of “unnecessary” interventions due to false-positive results. Even though breast cancer is the most common noncutaneous cancer in women, only a very small fraction (0.1% to 0.5%, depending on age) actually have the disease when they are screened. Therefore, even though the specificity of mammography exceeds 90%, most abnormal tests are false-positives.[1] Women with abnormal screening test results have additional procedures performed to determine whether the mammographic finding is cancer. These procedures include additional mammographic imaging (e.g., magnification of the area of concern), ultrasound, 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 on 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 actuarial 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.[2] 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.[3] Cumulative risk of at least one false-positive by the ninth mammogram varied from 5% to 100%, depending on four patient variables and three radiologic variables. Patient variables independently associated with increased chance of a false-positive result included younger age, higher number of previous breast biopsies, family history of breast cancer, and current estrogen use. Radiologic variables included longer time between screenings, failure to compare the current and previous mammograms, and the individual radiologist’s tendency to interpret mammograms as abnormal, which ranged from 2.6% to 24.4% across 93 radiologists in the study. Overall, the largest risk factor for having a false-positive mammogram was the individual radiologist’s tendency to read mammograms as abnormal. The authors noted that confidence intervals for estimates of false-positives beyond five mammograms were wide because of the relatively small numbers of women in the analysis with more than five mammograms.

By reviewing Medicare claims following mammographic screening in 23,172 women older than 65 years, one study [4] found that 85 per 1,000 had follow-up testing and 23 per 1,000 had biopsies. The cancer detection rate was 7 per 1,000, so the PPV for an abnormal mammogram was 8%. For women older than 70 years, the PPV was 14%. An audit of mammograms done 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 1 out of 30 of the cases referred for additional testing.[5]

The sensitivity of mammography (refer to the Mammography section) 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). If a woman does not seek medical attention for a breast symptom or if her physician is reluctant to evaluate that symptom because she has a “normal” mammogram, she may suffer adverse consequences. Whereas the medical community has been carefully educated that a negative diagnostic mammogram should not deter work-up of a palpable lump, the medical and lay communities should be made aware that a negative screening mammogram misses one in five cancers.

Because radiation exposure is a known risk factor for the development of breast cancer, it is ironic that ionizing radiation is our best screening tool. The major predictors of risk are young age at the time of radiation exposure and the radiation dose. For women older than 40 years, the benefits of annual mammograms may outweigh any potential risk of radiation exposure due to mammography.[6] It is speculated that certain subpopulations of women may have an inherited susceptibility to ionizing radiation damage,[7,8] but mammography has never been shown to be harmful in these, or any, subgroups. In the United States, the mean glandular dose for screening mammography is 1 mGy to 2 mGy (100–200 mrad) per view or 2 mGy to 4 mGy (200–400 mrad) per standard two-view exam.[9,10]

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.[11] Several studies,[12-14] however, show that the anxiety following evaluation of a false-positive test leads to increased participation in future screening examinations.

The purpose of screening for cancer is to detect cancer before it becomes symptomatic and to change the course of disease by treating the cancer early. Cancers do not progress at the same rate, however, and not all early-stage cancer treatment is successful.

Lesions exist that fulfill the histologic criteria of cancer but would neither progress nor become clinically apparent in a patient's lifetime. Data confirming this concept come from pathologic examination of normal breast tissue. An overview of seven autopsy studies documents a median prevalence of 1.3% for invasive breast cancer (range, 0%–1.8%) and 8.9% for ductal carcinoma in situ (range, 0%–14.7%).[15,16] Detection and treatment of these lesions constitute overdiagnosis and do not confer any benefit to the patient. It is currently impossible to distinguish with certainty the cancers that will progress from those that will not.

Therefore, one of the consequences of screening a population of women is the detection, in some women, of cancers that are destined to remain occult during their lifetimes. When these clinically insignificant cancers are detected, there is no benefit, yet these women will undergo treatments such as surgery, radiation therapy, hormonal therapy, and chemotherapy. It is difficult to determine the proportion of screen-detected cancers that fall into this category.

Population-based comparisons of breast cancer incidence before and after adoption of screening suggest that overdiagnosis is a substantial problem.[17-21] One might expect that screening will have identified cancers earlier and that a rise in incidence rates would be followed by a subsequent compensatory decline. This, however, has not been observed. Cancer incidence rates increase substantially in screened populations, without a compensatory drop in later years. For example, in Sweden, the age-specific incidence rates doubled between 1986 and 2002 for all age groups participating in screening.[17] Another study in 11 rural Swedish counties documented a persistent increase in breast cancer incidence following the advent of screening.[18] A population-based study from Norway and Sweden 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 age 69 years was ever seen.[22] Similar findings suggestive of overdiagnosis have been reported from the United Kingdom [19] and the United States.[20,21] Approximations of the magnitude of the problem of overdiagnosis range from 10% to 30% of newly diagnosed breast cancer cases, depending on utilization and intensity of screening.[23,24]

References

1. Kerlikowske K, Grady D, Barclay J, et al.: Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 270 (20): 2444-50, 1993.  [PUBMED Abstract]
   
   
2. Elmore JG, Barton MB, Moceri VM, et al.: Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 338 (16): 1089-96, 1998.  [PUBMED Abstract]
   
   
3. Christiansen CL, Wang F, Barton MB, et al.: Predicting the cumulative risk of false-positive mammograms. J Natl Cancer Inst 92 (20): 1657-66, 2000.  [PUBMED Abstract]
   
   
4. Welch HG, Fisher ES: Diagnostic testing following screening mammography in the elderly. J Natl Cancer Inst 90 (18): 1389-92, 1998.  [PUBMED Abstract]
   
   
5. Rosen EL, Baker JA, Soo MS: Malignant lesions initially subjected to short-term mammographic follow-up. Radiology 223 (1): 221-8, 2002.  [PUBMED Abstract]
   
   
6. Feig SA, Ehrlich SM: Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits. Radiology 174 (3 Pt 1): 638-47, 1990.  [PUBMED Abstract]
   
   
7. Helzlsouer KJ, Harris EL, Parshad R, et al.: Familial clustering of breast cancer: possible interaction between DNA repair proficiency and radiation exposure in the development of breast cancer. Int J Cancer 64 (1): 14-7, 1995.  [PUBMED Abstract]
   
   
8. Swift M, Morrell D, Massey RB, et al.: Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325 (26): 1831-6, 1991.  [PUBMED Abstract]
   
   
9. Kopans DB: Mammography and radiation risk. In: Janower ML, Linton OW, eds.: Radiation Risk: a Primer. Reston, Va: American College of Radiology, 1996, pp 21-22. 
   
   
10. Suleiman OH, Spelic DC, McCrohan JL, et al.: Mammography in the 1990s: the United States and Canada. Radiology 210 (2): 345-51, 1999.  [PUBMED Abstract]
    
    
11. Lerman C, Trock B, Rimer BK, et al.: Psychological side effects of breast cancer screening. Health Psychol 10 (4): 259-67, 1991.  [PUBMED Abstract]
    
    
12. Gram IT, Lund E, Slenker SE: Quality of life following a false positive mammogram. Br J Cancer 62 (6): 1018-22, 1990.  [PUBMED Abstract]
    
    
13. Burman ML, Taplin SH, Herta DF, et al.: Effect of false-positive mammograms on interval breast cancer screening in a health maintenance organization. Ann Intern Med 131 (1): 1-6, 1999.  [PUBMED Abstract]
    
    
14. Pisano ED, Earp J, Schell M, et al.: Screening behavior of women after a false-positive mammogram. Radiology 208 (1): 245-9, 1998.  [PUBMED Abstract]
    
    
15. Welch HG, Black WC: Using autopsy series to estimate the disease "reservoir" for ductal carcinoma in situ of the breast: how much more breast cancer can we find? Ann Intern Med 127 (11): 1023-8, 1997.  [PUBMED Abstract]
    
    
16. Black WC, Welch HG: Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med 328 (17): 1237-43, 1993.  [PUBMED Abstract]
    
    
17. Hemminki K, Rawal R, Bermejo JL: Mammographic screening is dramatically changing age-incidence data for breast cancer. J Clin Oncol 22 (22): 4652-3, 2004.  [PUBMED Abstract]
    
    
18. Jonsson H, Johansson R, Lenner P: Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden. Int J Cancer 117 (5): 842-7, 2005.  [PUBMED Abstract]
    
    
19. Johnson A, Shekhdar J: Breast cancer incidence: what do the figures mean? J Eval Clin Pract 11 (1): 27-31, 2005.  [PUBMED Abstract]
    
    
20. White E, Lee CY, Kristal AR: Evaluation of the increase in breast cancer incidence in relation to mammography use. J Natl Cancer Inst 82 (19): 1546-52, 1990.  [PUBMED Abstract]
    
    
21. Feuer EJ, Wun LM: How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach. Am J Epidemiol 136 (12): 1423-36, 1992.  [PUBMED Abstract]
    
    
22. Zahl PH, Strand BH, Maehlen J: Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 328 (7445): 921-4, 2004.  [PUBMED Abstract]
    
    
23. Gøtzsche PC, Nielsen M: Screening for breast cancer with mammography. Cochrane Database Syst Rev (4): CD001877, 2006.  [PUBMED Abstract]
    
    
24. Zackrisson S, Andersson I, Janzon L, et al.: Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study. BMJ 332 (7543): 689-92, 2006.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >