Breast Cancer Screening Concepts
Numerous uncontrolled trials and retrospective series have documented the ability of mammography to diagnose small, early-stage breast cancers, which have a favorable clinical course. Although several trials also show better cancer-related survival in screened versus nonscreened women, a number of important biases may explain that finding:
- Lead-time bias: Survival time for a cancer found mammographically includes the time between detection and the time when the cancer would have been detected because of clinical symptoms, but this time is not included in the survival time of cancers found because of symptoms.
- Length bias: Mammography detects a cancer while it is preclinical, and preclinical durations vary. Cancers with longer preclinical durations are, by definition, present during more opportunities for discovery and therefore are more likely to be detected by screening; these cancers tend to be slow growing and to have better prognoses, irrespective of screening.
- Overdiagnosis bias: An extreme form of length bias; screening may find cancers that are very slow growing and would never have become manifest clinically in the woman’s lifetime.
- Healthy volunteer bias: The screened population may be the healthiest and/or the most health-conscious women in the general population.
Because the extent of these biases is never clear in any particular study, most groups rely on randomized controlled trials to assess the benefits of screening. (Refer to the Cancer Screening Summary Overview for more information.)
Assessment of Performance and Accuracy
Performance benchmarks for screening mammography in the United States are described on the Breast Cancer Surveillance Consortium (BCSC) Web site.
The sensitivity of mammography is the percentage of breast cancers detected in a given population, when breast cancer is present. Sensitivity depends on tumor size, conspicuity, and hormone sensitivity as well as breast tissue density, patient age, timing within the menstrual cycle, overall image quality, and interpretive skill of the radiologist. Overall sensitivity is approximately 79% but is lower in younger women and in those with dense breast tissue (see the BCSC Web site).[2-4] Delay in diagnosis of breast cancer is the most common cause of medical malpractice litigation and half of the cases resulting in payment to the claimant involve false-negative mammograms.
Specificity and false-positive rate
The specificity of mammography is the likelihood of the test being normal when cancer is absent, whereas the false-positive rate is the likelihood of the test being abnormal when cancer is absent. If specificity is low, many false-positive examinations result in unnecessary follow-up examinations and procedures. (Refer to the subsection on Harms in the Screening With Mammography section of the Overview section of this summary for more information.)
Interval cancers are cancers that are diagnosed in the interval after a normal screening examination and before the subsequent screen. Some of these cancers were present at the time of mammography (false-negatives), and others grew rapidly in the interval between mammography and detection. As a general rule, interval cancers have characteristics of rapid growth [6,7] and are frequently of advanced stage at the time of discovery/diagnosis.
One study of 576 women with interval cancers reported that interval cancers are more prevalent in women aged 40 to 49 years. Interval cancers appearing within 12 months of a negative screening mammogram appear to be related to decreased mammographic sensitivity, attributable to greater breast density in 68% of cases. Those appearing within a 24-month interval appear to be related both to decreased mammographic sensitivity due to greater breast density in 37.6% and to rapid tumor growth in 30.6%.
Another study that compared the characteristics of 279 screen-detected cancers with those of 150 interval cancers found that interval cancers were much more likely to occur in women younger than 50 years and to be of mucinous or lobular histology; or to have high histologic grade, high proliferative activity, relatively benign features mammographically and/or to lack calcifications. Screen-detected cancers were more likely to have tubular histology; to be smaller, low stage, and hormone sensitive; and to have a major component of ductal carcinoma in situ.
- Moody-Ayers SY, Wells CK, Feinstein AR: "Benign" tumors and "early detection" in mammography-screened patients of a natural cohort with breast cancer. Arch Intern Med 160 (8): 1109-15, 2000. [PUBMED Abstract]
- Carney PA, Miglioretti DL, Yankaskas BC, et al.: Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med 138 (3): 168-75, 2003. [PUBMED Abstract]
- Rosenberg RD, Hunt WC, Williamson MR, et al.: Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico. Radiology 209 (2): 511-8, 1998. [PUBMED Abstract]
- Kerlikowske K, Grady D, Barclay J, et al.: Likelihood ratios for modern screening mammography. Risk of breast cancer based on age and mammographic interpretation. JAMA 276 (1): 39-43, 1996. [PUBMED Abstract]
- Physician Insurers Association of America: Breast Cancer Study. Washington, DC: Physician Insurers Association of America, 1995.
- Porter PL, El-Bastawissi AY, Mandelson MT, et al.: Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 91 (23): 2020-8, 1999. [PUBMED Abstract]
- Hakama M, Holli K, Isola J, et al.: Aggressiveness of screen-detected breast cancers. Lancet 345 (8944): 221-4, 1995. [PUBMED Abstract]
- Tabár L, Faberberg G, Day NE, et al.: What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 55 (5): 547-51, 1987. [PUBMED Abstract]
- Buist DS, Porter PL, Lehman C, et al.: Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst 96 (19): 1432-40, 2004. [PUBMED Abstract]