Interval cancers

Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor. Copyright 2007 Massachusetts Medical Society.

Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). Mammographic breast density appears to be a major risk factor for interval cancer.

To (a) determine the performance of screening mammography, ultrasonography (US), and physical examination (PE); (b) analyze the influence of age, hormonal status, and breast density; (c) compare the size and stage of tumors detected with each modality; and (d) determine which modality or combination of modalities optimize cancer detection. A total of 11,130 asymptomatic women underwent 27,825 screening sessions, (mammography and subsequent PE). Women with dense breasts subsequently underwent screening US. Abnormalities were deemed positive if biopsy findings revealed malignancy and negative if findings from biopsy or all screening examinations were negative. In 221 women, 246 cancers were found. Sensitivity, specificity, negative and positive predictive values, and accuracy of mammography were 77.6%, 98.8%, 99.8%, 35.8%, and 98.6%, respectively; those of PE, 27.6%, 99.4%, 99.4%, 28.9%, and 98.8%, respectively; and those of US, 75.3%, 96.8%, 99.7%, 20.5%, and 96.6%, respectively. Screening breast US increased the number of women diagnosed with nonpalpable invasive cancers by 42% (30 of 71). Mammographic sensitivity declined significantly with increasing breast density (P <.01) (48% for the densest breasts) and in younger women with dense breasts (P =.02); the effects were independent. Mammography and US together had significantly higher sensitivity (97%) than did mammography and PE together (74%) (P <.001). Tumors detected at mammography and/or US were significantly smaller (P =.01) and of lower stage (P =.01) than those detected at PE. Mammographic sensitivity for breast cancer declines significantly with increasing breast density and is independently higher in older women with dense breasts. Addition of screening US significantly increases detection of small cancers and depicts significantly more cancers and at smaller size and lower stage than does PE, which detects independently extremely few cancers. Hormonal status has no significant effect on effectiveness of screening independent of breast density.