Proceedings of the consensus conference on breast conservation, Milan, Italy, April 28-May 1, 2005.
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Biomedical subjects
Publications and source records attributed to Roland Holland.
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BACKGROUND: The recall rate (i.e., the rate at which mammographically screened women are recalled for additional assessment) in the Dutch breast screening program (0.89% in 2000 for subsequent examinations) is the lowest worldwide, with possible consequences including higher rates of late-detected (i.e., "missed") interval and screen-detected cancers. To estimate the effect of changes in recall rate on earlier detection of cancers, we carried out a blinded review of interval and screen-detected cancers in the Dutch screening program. METHODS: A total of 495 sets of screen-negative mammograms (prediagnostic mammogram and the immediate previous mammogram) were collected from women participating in the biennial Dutch screening program. Of these, 250 were from control subjects, and 245 were from women who were subsequently diagnosed with breast cancer (123 interval and 122 screen-detected cancers). These mammograms were read by 15 radiologists who specialize in screening mammography and were blinded to outcome. Mean detection sensitivities for different false-positive rates were calculated using a linear mixed model. These results were used to calculate the effect of recall rate adjustment on earlier detection of cancers and numbers of false-positives. RESULTS: Increasing the recall rate to 2.0% would increase the detection rate from 4.20 per thousand to 4.52 per thousand due to the earlier detection of interval cancers. Moreover, 0.54 per thousand of the screen-detected cancers would be detected 2 years earlier (late screen-detected cancers). At recall rates of 3.0% and 4.0% the detection rate would increase to 4.58 per thousand and 4.63 per thousand, respectively, and 0.64 per thousand and 0.72 per thousand, respectively, of the screen-detected cancers would be detected 2 years earlier. For each 1.0% incremental increase in recall rate above 5.0%, the detection rate would increase by approximately 0.03 per thousand, with positive predictive values decreasing to below 10%. CONCLUSION: Breast cancer can be detected earlier by lowering the threshold for recall, especially for recall rates of 1%-4%. With further recall rate increases, cancer detection levels off with a disproportionate increase of false-positive rates.
The purpose of this study was to determine the importance of using prior mammograms for classification of benign and malignant masses. Five radiologists and one resident classified mass lesions in 198 mammograms obtained from a population-based screening program. Cases were interpreted twice, once without and once with comparison of previous mammograms, in a sequential reading order using soft copy image display. The radiologists' performances in classifying benign and malignant masses without and with previous mammograms were evaluated with receiver operating characteristic (ROC) analysis. The statistical significance of the difference in performances was calculated using analysis of variance. The use of prior mammograms improved the classification performance of all participants in the study. The mean area under the ROC curve of the readers increased from 0.763 to 0.796. This difference in performance was statistically significant (P = 0.008).
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PURPOSE: To evaluate the use of a computer-aided detection (CAD) system (designed for mammographic mass detection) to help improve mass interpretation and to compare CAD results with independent double-reading results. MATERIALS AND METHODS: Screening mammograms from 500 cases were collected; 125 of these cases were screening-detected cancers, and 125 were interval cancers. Previously obtained screening mammograms (ie, prior mammograms) were available in all cases. All mammograms were analyzed by a CAD system, which detected mass regions and assigned a level of (cancer) suspicion to each mass. Ten experienced screening radiologists read the prior mammograms. For independent interpretation with CAD, the suspicion rating assigned to each finding by the radiologist was weighted with the CAD output at the area of the finding. CAD markers on areas that were not reported by the radiologist were not used. Independent double reading was implemented by using a rule to combine the levels of suspicion assigned to findings by two radiologists. Results were evaluated by using localized-response receiver operating characteristic analysis. RESULTS: In a total of 141 cases, there was a visible abnormality at the location of the cancer on the prior mammogram, and 115 of these were classified as mass cases. For prior mammograms that depicted masses, the mean sensitivity of the radiologists, as averaged among the false-positive rates lower than 10%, was 39.4%; this increased by 7.0% with CAD and by 10.5% with double reading. Differences among single, double, and CAD readings were statistically significant (P <.001). CONCLUSION: Although independent double reading yields the best detection performance, the presence and probability of CAD mass markers can improve mammogram interpretation.
Breast biology and pathology are currently shaped by the two-cell concept that recognizes only glandular and myoepithelial cells. In the present study, we have visualized a previously unidentified cell population within the epithelial compartment of the breast, which displays the phenotypic characteristics of a committed stem cell. Immunofluorescence double labeling with digital image processing and Western blotting were applied to normal breast tissue as well as to noninvasive and invasive breast cancers using antibodies to basal cytokeratin 5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle alpha-actin (SMA) as markers for myoepithelial cells (SMA). A distinct population of cells was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our experiments clearly demonstrate a precursor or committed stem cell function of the Ck5-positive cell that is responsible for regeneration of the human adult breast epithelium. However, the observation that the vast majority of breast cancers display the glandular epithelial immunophenotype strongly suggests that the neoplastic cells derive from a late stage of the glandular epithelial differentiation pathway. The significance of this new cell biological model is that it might serve as a tool to unravel the regulatory mechanisms that govern regeneration and abnormal proliferation of breast epithelium at the cellular level.
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