Mammography—Variables Associated with Accuracy
Prevalent Versus Subsequent Examination and the Interval Between Exams
Mammography and Computer-Aided Detection (CAD)
Several characteristics of women being screened that are associated with the accuracy of mammography include age, breast density, whether it is the first or subsequent exam, and time since last mammogram. Younger women have lower sensitivity and higher false-positive rates on screening mammography than do older women (refer to the Breast Cancer Surveillance Consortium performance measures by age for more information).
For women of all ages, high breast density is associated with 10% to 29% lower sensitivity. High breast density is an inherent trait, which can be familial [2,3] but also may be affected by age, endogenous  and exogenous [5,6] hormones, selective estrogen receptor modulators such as tamoxifen, and diet. Hormone therapy is associated with increased breast density and is associated not only with lower sensitivity but also with an increased rate of interval cancers.
The Million Women Study in the United Kingdom revealed three patient characteristics that were associated with decreased sensitivity and specificity of screening mammograms in women aged 50 to 64 years: use of postmenopausal hormone therapy, prior breast surgery, and body mass index below 25. In addition, a longer interval since the last mammogram increases sensitivity, recall rate, and cancer detection rate and decreases specificity.
Strategies have been proposed to improve mammographic sensitivity by altering diet, timing mammograms with menstrual cycles, interrupting hormone therapy before the examination, or using digital mammography machines. Obese women have more than a 20% increased risk of having false-positive mammography results compared with underweight and normal weight women, although sensitivity is unchanged.Tumor Characteristics
Some cancers are more easily detected by mammography than other cancers are. In particular, mucinous, lobular, and rapidly growing cancers can be missed because their appearance on x-rays is similar to that of normal breast tissue. Medullary carcinomas may be similarly missed. Some cancers, particularly those associated with BRCA1/2 mutations, masquerade as benign tumors.[17,18]Physician Characteristics
Radiologist performance is critical to assessing mammographic interpretive performance, yet there is substantial, well-documented variability among radiologists. Factors that influence radiologists’ performance include their level of experience and the volume of mammograms they interpret. There is often a trade-off between sensitivity and specificity, such that higher sensitivity may be associated with lower specificity. Radiologists in academic settings have a higher positive predictive value (PPV) of their recommendations to undergo biopsy than do community radiologists. Fellowship training in breast imaging may lead to improved cancer detection, but it is associated with higher false-positive rates.Facility Characteristics
After controlling for patient and radiologist characteristics, screening mammography interpretive performance (specificity, PPV, area under the curve [AUC]) varies by facility and is associated with facility-level characteristics. Higher interpretive accuracy of screening mammography was seen at facilities that offered screening examinations alone, included a breast imaging specialist on staff, did single as opposed to double readings, and reviewed interpretive audits two or more times each year.
False-positive rates vary significantly between facilities performing diagnostic mammography and are higher at facilities where concern about malpractice is high. False-positive rates are also higher at facilities serving vulnerable women (women of racial or ethnic minorities and women with lower educational attainment, limited household income, or rural residence) than at facilities serving nonvulnerable women, perhaps because of poorer compliance with recommendations for follow-up examinations. Analyses that do not adjust for important patient characteristics may falsely conclude that there is more facility variation in overall accuracy than actually exists.International Comparisons
International comparisons of screening mammography have found higher specificity in countries with more highly centralized screening systems and national quality assurance programs.[24,25] For example, one study reported that the recall rate is twice as high in the United States as it is in the United Kingdom, yet there is no difference in the rate of cancers detected. Such comparisons may be confounded by social, cultural, and economic factors.Prevalent Versus Subsequent Examination and the Interval Between Exams
The likelihood of diagnosing cancer is highest with the prevalent (first) screening examination, ranging from 9 to 26 cancers per 1,000 screens, depending on the woman’s age. The likelihood decreases for follow-up examinations, ranging from 1 to 3 cancers per 1,000 screens. The optimal interval between screening mammograms is unknown. In particular, the breast cancer mortality-focused, randomized, controlled trials used single screening intervals with little variability across the trials. A prospective United Kingdom trial randomly assigned women aged 50 to 62 years to receive mammograms annually or at the standard 3-year interval. Although the grade and node status were similar in both groups, more cancers of slightly smaller size were detected in the annual screening group, with a lead time of approximately 7 months in comparison with triennial screening.
A large observational study found a slightly increased risk of late-stage disease at diagnosis for women in their 40s who were adhering to a 2-year versus a 1-year schedule (28% vs. 21%; odds ratio (OR) = 1.35; 95% confidence interval [CI], 1.01–1.81), but no difference was seen for women in their 50s or 60s.[28,29]
A Finnish study of 14,765 women aged 40 to 49 years assigned women born in even-numbered years to annual screens and women born in odd-numbered years to triennial screens. The study was small in terms of number of deaths, with low power to discriminate breast cancer mortality between the two groups. There were 18 deaths from breast cancer in 100,738 life-years in the triennial screening group and 18 deaths from breast cancer in 88,780 life-years in the annual screening group (hazard ratio, 0.88; 95% CI, 0.59–1.27).Digital Mammography
Digital mammography is more expensive than screen-film mammography (SFM) but is more amenable to data storage and sharing. Performance of both technologies has been compared directly in several trials yielding similar results.
A large cohort of women (n = 42,760) who underwent both digital and film mammography was evaluated at 33 U.S. centers in the Digital Mammographic Imaging Screening Trial (DMIST). No differences in breast cancer detection were observed (AUC of 0.78 +/- 0.02 for digital and AUC of 0.74 +/- 0.02 for film; P = .18). Digital mammography was better at cancer detection in women younger than 50 years (AUC of 0.84 +/- 0.03 for digital; AUC of 0.69 +/- 0.05 for film; P = .002). A second DMIST report found that film mammography had a higher AUC in women aged 65 years and older (AUC 0.88 for film; AUC 0.70 for digital; P = .025); however, this finding was not statistically significant when the multiple comparisons were considered. In a large U.S. cohort study, sensitivity for women younger than 50 years was 75.7% (95% CI, 71.7–79.3) for film mammography and 82.4% (95% CI, 76.3–87.5) for digital mammography; specificity was 89.7% (95% CI, 89.6–89.8) for film mammography and 88.0% (95% CI, 88.2–87.8) for digital mammography. A comparison of the findings from 1.5 million digital mammography screens and 4.5 million SFM screens that occurred in the Netherlands from 2004 to 2010 indicated higher recall and detection rates for the digital mammography screens. Among radiologists who read both digital and SFM exams (n = 1.5 million), the recall rates were 2.0% for digital mammography (95% CI, 2.0–2.1) versus 1.6% for SFM (95% CI, 1.6–1.6); the detection rates were 5.9 per 1,000 (95% CI, 5.7–6.0) for digital mammography and 5.1 per 1,000 (95% CI, 5.0–5.2) for SFM. The PPV was statistically significantly lower in the digital mammography group (PPV, 31.2%; 95% CI, 30.6–31.7) than in the screen-film group (PPV, 34.4%; 95% CI, 33.8%–35.0%). For women aged 49 to 54 years, recall rates were 2.7% (digital) versus 2.0% (film); detection rates were 5.1% (digital) versus 4.0% (film); and PPV was 21.4% (digital) versus 22.1% (film). For women aged 55 to 74 years, recall rates were 1.7% (digital) versus 1.4% (film); detection rates were 6.2% (digital) versus 5.6% (film); and PPV was 35.7% (digital) versus 40.1% (film). Findings for SFM exams (n = 4.5 million) read by radiologists who read only SFM exams were similar to the findings for SFM exams read by radiologists who read both types of mammography exams.
A meta-analysis  of 10 studies, including the DMIST [13,31] and the aforementioned U.S. cohort study, compared digital mammography with film mammography in 82,573 women who underwent both types of the exam. In a random-effects model, there was no statistically significant difference in cancer detection between the two types of mammography (AUC of 0.92 for film and AUC of 0.91 for digital). For women younger than 50 years, all studies found that sensitivity was higher for digital mammography but that specificity was either the same or higher for film mammography. The meta-analysis found no other differences based on age.
Computed radiography (CR) utilizes a cassette-based removable detector and external reading device to generate a digital image. A large concurrent cohort study compared 254,758 full-field digital mammography (FFDM) screens with 487,334 SFM screens and 74,190 CR screens. Again, the cancer detection rate was not different between FFDM (4.9 per 1,000) and SFM (4.8 per 1,000), although the recall rate was higher for FFDM. Importantly, cancer detection was lower for CR at 3.4 per 1,000, adjusted OR 0.79 (95% CI, 0.68–0.93). Two prior studies of noncontemporaneous cohorts showed no difference between CR and SFM or higher cancer detection rate from CR.[36,37]Mammography and Computer-Aided Detection (CAD)
CAD systems are designed to help radiologists read mammograms by highlighting suspicious regions such as clustered microcalcifications and masses. Generally, CAD systems increase sensitivity and decrease specificity  and increase detection of ductal carcinoma in situ (DCIS). Several CAD systems are in use. One large population-based study comparing recall rates and breast cancer detection rates before and after the introduction of CAD systems found no change in either rate.[38,41] Another large study noted an increase in recall rate and increased DCIS detection but no improvement in invasive cancer detection rate.[40,42]References
- 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]
- Pankow JS, Vachon CM, Kuni CC, et al.: Genetic analysis of mammographic breast density in adult women: evidence of a gene effect. J Natl Cancer Inst 89 (8): 549-56, 1997. [PUBMED Abstract]
- Boyd NF, Dite GS, Stone J, et al.: Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347 (12): 886-94, 2002. [PUBMED Abstract]
- White E, Velentgas P, Mandelson MT, et al.: Variation in mammographic breast density by time in menstrual cycle among women aged 40-49 years. J Natl Cancer Inst 90 (12): 906-10, 1998. [PUBMED Abstract]
- Harvey JA, Pinkerton JV, Herman CR: Short-term cessation of hormone replacement therapy and improvement of mammographic specificity. J Natl Cancer Inst 89 (21): 1623-5, 1997. [PUBMED Abstract]
- Laya MB, Larson EB, Taplin SH, et al.: Effect of estrogen replacement therapy on the specificity and sensitivity of screening mammography. J Natl Cancer Inst 88 (10): 643-9, 1996. [PUBMED Abstract]
- Baines CJ, Dayan R: A tangled web: factors likely to affect the efficacy of screening mammography. J Natl Cancer Inst 91 (10): 833-8, 1999. [PUBMED Abstract]
- Brisson J, Brisson B, Coté G, et al.: Tamoxifen and mammographic breast densities. Cancer Epidemiol Biomarkers Prev 9 (9): 911-5, 2000. [PUBMED Abstract]
- Boyd NF, Greenberg C, Lockwood G, et al.: Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group. J Natl Cancer Inst 89 (7): 488-96, 1997. [PUBMED Abstract]
- Crouchley K, Wylie E, Khong E: Hormone replacement therapy and mammographic screening outcomes in Western Australia. J Med Screen 13 (2): 93-7, 2006. [PUBMED Abstract]
- Banks E, Reeves G, Beral V, et al.: Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study. BMJ 329 (7464): 477, 2004. [PUBMED Abstract]
- Yankaskas BC, Taplin SH, Ichikawa L, et al.: Association between mammography timing and measures of screening performance in the United States. Radiology 234 (2): 363-73, 2005. [PUBMED Abstract]
- Pisano ED, Gatsonis C, Hendrick E, et al.: Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med 353 (17): 1773-83, 2005. [PUBMED Abstract]
- Elmore JG, Carney PA, Abraham LA, et al.: The association between obesity and screening mammography accuracy. Arch Intern Med 164 (10): 1140-7, 2004. [PUBMED Abstract]
- 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]
- Wallis MG, Walsh MT, Lee JR: A review of false negative mammography in a symptomatic population. Clin Radiol 44 (1): 13-5, 1991. [PUBMED Abstract]
- Tilanus-Linthorst M, Verhoog L, Obdeijn IM, et al.: A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography. Int J Cancer 102 (1): 91-5, 2002. [PUBMED Abstract]
- Ganott MA, Harris KM, Klaman HM, et al.: Analysis of False-Negative Cancer Cases Identified with a Mammography Audit. Breast J 5 (3): 166-175, 1999. [PUBMED Abstract]
- Elmore JG, Jackson SL, Abraham L, et al.: Variability in interpretive performance at screening mammography and radiologists' characteristics associated with accuracy. Radiology 253 (3): 641-51, 2009. [PUBMED Abstract]
- Meyer JE, Eberlein TJ, Stomper PC, et al.: Biopsy of occult breast lesions. Analysis of 1261 abnormalities. JAMA 263 (17): 2341-3, 1990. [PUBMED Abstract]
- Taplin S, Abraham L, Barlow WE, et al.: Mammography facility characteristics associated with interpretive accuracy of screening mammography. J Natl Cancer Inst 100 (12): 876-87, 2008. [PUBMED Abstract]
- Jackson SL, Taplin SH, Sickles EA, et al.: Variability of interpretive accuracy among diagnostic mammography facilities. J Natl Cancer Inst 101 (11): 814-27, 2009. [PUBMED Abstract]
- Goldman LE, Walker R, Miglioretti DL, et al.: Accuracy of diagnostic mammography at facilities serving vulnerable women. Med Care 49 (1): 67-75, 2011. [PUBMED Abstract]
- Smith-Bindman R, Chu PW, Miglioretti DL, et al.: Comparison of screening mammography in the United States and the United kingdom. JAMA 290 (16): 2129-37, 2003. [PUBMED Abstract]
- Elmore JG, Nakano CY, Koepsell TD, et al.: International variation in screening mammography interpretations in community-based programs. J Natl Cancer Inst 95 (18): 1384-93, 2003. [PUBMED Abstract]
- 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]
- The Breast Screening Frequency Trial Group: The frequency of breast cancer screening: results from the UKCCCR Randomised Trial. United Kingdom Co-ordinating Committee on Cancer Research. Eur J Cancer 38 (11): 1458-64, 2002. [PUBMED Abstract]
- White E, Miglioretti DL, Yankaskas BC, et al.: Biennial versus annual mammography and the risk of late-stage breast cancer. J Natl Cancer Inst 96 (24): 1832-9, 2004. [PUBMED Abstract]
- Mandelblatt JS, Cronin KA, Bailey S, et al.: Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med 151 (10): 738-47, 2009. [PUBMED Abstract]
- Parvinen I, Chiu S, Pylkkänen L, et al.: Effects of annual vs triennial mammography interval on breast cancer incidence and mortality in ages 40-49 in Finland. Br J Cancer 105 (9): 1388-91, 2011. [PUBMED Abstract]
- Pisano ED, Hendrick RE, Yaffe MJ, et al.: Diagnostic accuracy of digital versus film mammography: exploratory analysis of selected population subgroups in DMIST. Radiology 246 (2): 376-83, 2008. [PUBMED Abstract]
- Kerlikowske K, Hubbard RA, Miglioretti DL, et al.: Comparative effectiveness of digital versus film-screen mammography in community practice in the United States: a cohort study. Ann Intern Med 155 (8): 493-502, 2011. [PUBMED Abstract]
- van Luijt PA, Fracheboud J, Heijnsdijk EA, et al.: Nation-wide data on screening performance during the transition to digital mammography: observations in 6 million screens. Eur J Cancer 49 (16): 3517-25, 2013. [PUBMED Abstract]
- Souza FH, Wendland EM, Rosa MI, et al.: Is full-field digital mammography more accurate than screen-film mammography in overall population screening? A systematic review and meta-analysis. Breast 22 (3): 217-24, 2013. [PUBMED Abstract]
- Chiarelli AM, Edwards SA, Prummel MV, et al.: Digital compared with screen-film mammography: performance measures in concurrent cohorts within an organized breast screening program. Radiology 268 (3): 684-93, 2013. [PUBMED Abstract]
- Heddson B, Rönnow K, Olsson M, et al.: Digital versus screen-film mammography: a retrospective comparison in a population-based screening program. Eur J Radiol 64 (3): 419-25, 2007. [PUBMED Abstract]
- Lipasti S, Anttila A, Pamilo M: Mammographic findings of women recalled for diagnostic work-up in digital versus screen-film mammography in a population-based screening program. Acta Radiol 51 (5): 491-7, 2010. [PUBMED Abstract]
- Gur D, Sumkin JH, Rockette HE, et al.: Changes in breast cancer detection and mammography recall rates after the introduction of a computer-aided detection system. J Natl Cancer Inst 96 (3): 185-90, 2004. [PUBMED Abstract]
- Ciatto S, Del Turco MR, Risso G, et al.: Comparison of standard reading and computer aided detection (CAD) on a national proficiency test of screening mammography. Eur J Radiol 45 (2): 135-8, 2003. [PUBMED Abstract]
- Fenton JJ, Taplin SH, Carney PA, et al.: Influence of computer-aided detection on performance of screening mammography. N Engl J Med 356 (14): 1399-409, 2007. [PUBMED Abstract]
- Elmore JG, Carney PA: Computer-aided detection of breast cancer: has promise outstripped performance? J Natl Cancer Inst 96 (3): 162-3, 2004. [PUBMED Abstract]
- Fenton JJ, Xing G, Elmore JG, et al.: Short-term outcomes of screening mammography using computer-aided detection: a population-based study of medicare enrollees. Ann Intern Med 158 (8): 580-7, 2013. [PUBMED Abstract]