Because the extent of these biases is never clear in any particular study, one must rely on randomized controlled trials to assess the benefits of screening. (Refer to the Effect of Screening on Breast Cancer Mortality section of this summary for more information.)
The sensitivity of mammography is the proportion of breast cancer detected when breast cancer is present. Sensitivity depends on several factors, including lesion size, lesion conspicuity, breast tissue density, patient age, the hormone status of the tumor, overall image quality, and interpretive skill of the radiologist. Sensitivity is of great importance to patients and physicians alike; failure to diagnose breast cancer is the most common cause of medical malpractice litigation. Half of the cases resulting in payment to the claimant had false-negative mammograms.
Overall sensitivity is approximately 79% but is lower in younger women and in those with dense breast tissue. Overall specificity is approximately 90% and is lower in younger women and in those with dense breasts (see the Breast Cancer Surveillance Consortium).[6,7,8] Using data from screened women in the Group Health Cooperative of Puget Sound health maintenance organization, characteristics of 150 cancers not detected at screening but diagnosed within 24 months of a normal screening examination (interval cancers) were compared with those of 279 screen-detected cancers. Interval cancers were much more likely to occur in women younger than 50 years and to be of mucinous or lobular histology, high histologic grade, and high proliferative activity. Screen-detected cancers were more likely to have tubular histology; to be smaller, of low stage, and hormone sensitive; and to have a major component of in situ cancer.
Mammography is a less sensitive test for women aged 40 to 49 years than for older women. The authors of one study examined 576 women who developed invasive breast cancer following a screening mammogram to determine whether greater breast density or faster growing tumors among younger women explained the lower sensitivity. They found that more younger women with cancer had developed interval cancers. They also found that greater breast density explained most (68%) of the decreased mammographic sensitivity in younger women at 12 months, whereas at 24 months, rapid tumor growth and breast density explained approximately equal proportions of the interval cancers.
Screen-detected cancers have a more favorable prognosis than do interval cancers, even when matched for size and stage; this is an expression of length bias. These cancers have favorable cellular characteristics, including lower histologic grade, higher rate of hormone sensitivity, and lower proliferative indices. A 10-year follow-up study of 1,983 Finnish women with invasive breast cancer demonstrated that the method of cancer detection is an independent prognostic variable. When controlled for age, node involvement, and tumor size, screen-detected cancers had a lower risk of relapse and better overall survival. The hazard ratio (HR) for death was 1.90 (95% confidence interval [CI], 1.15-3.11) for women whose cancers were detected outside screening, even though they were more likely to get adjuvant systemic therapy. Similarly, an examination of the breast cancers found in three randomized screening trials (Health Insurance Plan, National Breast Screening Study [NBSS]-1, and NBSS-2-see below) accounted for stage, nodal status, and tumor size and determined that patients whose cancer was found via screening enjoyed a more favorable prognosis. Namely, the HRs for death were 1.53 (95% CI, 1.17-2.00) for interval and incident cancers in comparison with screen-detected cancers and 1.36 (95% CI, 1.10-1.68) for cancers in the control group in comparison with screen-detected cancers. A third study compared the outcomes of 5,604 English women with screen-detected or symptomatic breast cancers diagnosed between 1998 and 2003. After controlling for tumor size, nodal status, grade, and patient age, researchers found that the women with symptomatic cancers fared worse. The HR for survival was 0.79 (95% CI, 0.63-0.99). Thus, method of cancer detection is a powerful predictor of patient outcome, which is useful for prognostication and treatment decisions.