High-grade Ductal Carcinoma In Situ Lesions Research Articles

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

PurposeDuctal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) for the early diagnosis of DCIS.MethodsForty‐seven patients, including 25 with DCIS (age: 28–70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25–67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE‐MRI and IVIM‐DWI in this study. The quantitative parameters Ktrans, Kep, Ve, Vp, and D, f, D* were obtained by processing of DCE‐MRI and IVIM‐DWI images with Omni‐Kinetics and MITK‐Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares.ResultsAll low‐grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle‐grade and high‐grade DCIS lesions showed non‐mass‐like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans, Kep, and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans, Kep, D and the combined indicator of Ktrans, Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016).ConclusionDCE‐MRI and IVIM‐DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over‐treatment of benign lesions.

Comparison of Digital Screening Mammography and Screen-Film Mammography in the Early Detection of Clinically Relevant Cancers: A Multicenter Study

To compare screen-film mammography with digital mammography in a breast cancer screening program, with a focus on the clinical relevance of detected cancers. The study was approved by the regional medical ethics review board. Informed consent was not required. Before the nationwide transition to digital mammography in the Dutch biennial screening program, the performance of digital mammography was studied in three screening regions. For initial screening examinations, mediolateral oblique and craniocaudal views were obtained of each breast. In subsequent examinations, the mediolateral oblique view was standard. A craniocaudal view was added if indicated. Screening outcomes obtained with screen-film mammography and digital mammography, including radiologic and pathologic characteristics, were compared for initial and subsequent examinations. A total of 1,198,493 screening examinations were performed between 2003 and 2007. Recall was indicated in 18 896 cases (screen-film mammography: 2.6% at initial examinations, 1.3% at subsequent examinations; digital mammography: 4.4% at initial examinations, 2.1% at subsequent examinations; P < .001 for both). Breast cancer was diagnosed in 6410 women (detection rate per 1000 women with screen-film mammography: 5.6 at initial examinations, 5.2 at subsequent examinations; detection rate per 1000 women with digital mammography: 6.8 at initial examinations, 6.1 at subsequent examinations; P = .02 and P < .001, respectively). Digital mammography depicted significantly more ductal carcinoma in situ (DCIS) lesions, irrespective of screening round. Invasive carcinoma was detected significantly more often in subsequent examinations, particularly when associated with microcalcifications (P = .047). The distribution of the histopathologic differentiation grades for DCIS and invasive carcinoma were similar with both modalities. However, with digital mammography more high-grade DCIS lesions were detected at subsequent examinations (P = .013). In a population-based breast screening program, the performance of digital mammography in the detection of DCIS and invasive carcinoma was substantially better than that of screen-film mammography. There is no sign of an increase in detection of low-grade DCIS lesions-indicative of possible overdiagnosis-with digital breast cancer screening. Rather, digital mammography appears to add to the detection of high-grade DCIS.

Lesion size is a major determinant of the mammographic features of ductal carcinoma in situ: findings from the Sloane project

To assess the radiological features of calcific ductal carcinoma in situ (DCIS) in a large, multicentre dataset according to grade and size, and to investigate the possibility that DCIS has different mammographic features when small. The dataset consisted of all Sloane Project DCIS cases where calcification was present mammographically and histological grade and size were available. The radiology data form classifies calcific DCIS as casting/linear, granular/irregular, or punctate. The pathology dataset includes cytonuclear grade and microscopic tumour size. Correlations were sought between the radiological findings and DCIS grade and size. The significance of differences was assessed using the chi-square test and chi-square test for trend. One thousand, seven hundred and eighty-three cases were included in the study. Of these, 1128, 485, and 170 had high, intermediate, and low-grade DCIS, respectively. Casting calcification was more frequently seen the higher the grade of DCIS, occurring in 58% of high grade, 38% of intermediate grade, and 26% of low-grade cases, respectively (p<0.001). Casting calcification was also increasingly common with increasing lesion size, irrespective of the histological grade (p<0.001). Thus casting calcifications in small (<10mm) high-grade DCIS lesions were seen with a similar frequency (50%) to those in moderate-sized (21-30 mm) intermediate-grade lesions (48%), and to those in large (>30 mm) low-grade lesions (46%). Lesion size has a strong influence on the radiological features of calcific DCIS; small, high-grade lesions often show no casting calcifications, whereas casting calcifications are seen in nearly half of large, low-grade lesions. As small clusters of punctate or granular calcifications may represent high-grade DCIS, an aggressive clinical approach to the diagnosis of such lesions is recommended as the adequate treatment of high-grade DCIS will prevent the occurrence of potentially life-threatening high-grade invasive disease.

HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer

The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a multivariate logistic regression were done to determine whether estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis, nuclear grade, lesion size, or patient age predicted the presence of associated invasive disease in patients with DCIS. Invasive foci were found in association with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not overexpress HER2. Although high nuclear grade, large lesion size, and HER2 overexpression were all associated with the presence of invasive disease on univariate analysis, HER2 was the only significant predictor for the presence of invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These data indicate that HER2 overexpression in DCIS lesions predicts the presence of invasive foci in patients with DCIS and suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression.

Contrast‐enhanced MRI of ductal carcinoma in situ: Characteristics of a new intensity‐modulated parametric mapping technique correlated with histopathologic findings

To identify morphologic and dynamic enhancement magnetic resonance imaging (MRI) features of pure ductal carcinoma in situ (DCIS) by using a new intensity-modulated parametric mapping technique, and to correlate the MRI features with histopathologic findings. Fourteen patients with pure DCIS on pathology underwent conventional mammography and contrast-enhanced (CE) MRI using the intensity-modulated parametric mapping technique. The MR images were reviewed and the lesions were categorized according to morphologic and kinetic criteria from the ACR BI-RADS-MRI Lexicon, with BI-RADS 4 and 5 lesions classified as suspicious. With the use of a kinetic curve shape analysis, MRI classified seven of 14 lesions (50%) as suspicious, including four with initial-rapid/late-washout and three with initial-rapid/late-plateau. Using morphologic criteria, MRI classified 10/14 (71%) as suspicious, with the most prominent morphologic feature being a regional enhancement pattern. Using the intensity modulated parametric mapping technique, MRI classified 12/14 cases (86%) as suspicious. Parametric mapping identified all intermediate- and high-grade DCIS lesions. The intensity-modulated parametric mapping technique for breast MRI resulted in the highest detection rate for the DCIS cases. Furthermore, the parametric mapping technique identified all intermediate- and high-grade DCIS lesions, suggesting that a negative MRI using the parametric mapping technique may exclude intermediate- and high-grade DCIS. This finding has potential clinical implications.

Ductal carcinoma in situ (DCIS): are we overdetecting it?

DCIS constitutes approximately one-quarter of screen-detected cancer. The proportion of screen-detected cancer that is DCIS decreases with the age of the screening population. Whether detecting DCIS at mammographic screening is of benefit depends on the natural history of the DCIS detected at screening and whether DCIS detection enables the detection of invasive foci already present within DCIS lesions. The natural history of DCIS varies according to the grade of the DCIS detected. The natural history of low grade DCIS is that approximately 60% of lesions will become invasive at 40 years follow-up. The natural history of high grade DCIS derived from local recurrence rates within high grade DCIS lesions, which have been inadequately resected and not given radiotherapy, suggests an invasive risk of at least 50% at 7 years follow-up. Given the average life expectancy of women with screen-detected DCIS is 25 years, this suggests high grade DCIS is an obligate precursor of invasive disease. There is a strong correlation between the grading of invasive cancer and the grade of DCIS from which it arose. This suggests that approximately 50% of low grade DCIS detected at screening will represent overdiagnosis while overdiagnosis of high grade DCIS would be rare. The natural history of intermediate grade DCIS is as yet unknown. Only 15% of screen-detected DCIS is low grade, suggesting that overdiagnosis is uncommon. Approximately 60% of screen-detected DCIS is high grade and in the vast majority of these patients adequate treatment will be preventing the occurrence of high grade invasive breast cancer. Approximately one-third of malignant calcification clusters detected at screening mammography already has an invasive focus. These invasive foci are usually small and high grade. Data gathered from all the units in the National Health Service Breast Screening Programme indicate a strong correlation between the detection of DCIS and the detection of small invasive cancers. These data indicate that for every two cases of DCIS detected, one case of a small invasive cancer is also detected. These data indicate that DCIS detection within a mammographic screening programme prevents the occurrence of high grade invasive cancer and aides the detection of small invasive cancers at a size where treatment can be successful. Overdiagnosis will occur in approximately one-half of the cases of low grade DCIS detected. This represents approximately 2% of screen-detected lesions. If one assumes the natural history of intermediate grade DCIS is intermediate between low and high grade disease then overdiagnosis of DCIS within a screening programme may represent 3% of screen-detected lesions.

Trends and predictors of size and grade for ductal carcinoma in situ (DCIS) in BreastScreen Victoria

Previous studies have examined predictors, such as hormone replacement therapy (HRT) use, of size and grade of invasive breast cancer, but little is known about factors that influence prognostic features of DCIS. We evaluated factors associated with size and grade of DCIS in a large screening programme, BreastScreen Victoria. A total of 1127 women were diagnosed with DCIS and 5301 with invasive breast cancer in BreastScreen Victoria between 1993 and 2000. We used multiple linear regression to evaluate predictors of size and multinomial logistic regression to evaluate predictors of grade. The ratio of DCIS to invasive tumours decreased with age but did not differ by time since the last screen. Older age (over 70 years) was associated with smaller DCIS size and better differentiated tumours (P = 0.05) compared with women aged 50–69 years. A longer screening interval was associated with larger DCIS tumours (P = 0.01) but was not associated with grade of DCIS. There was a borderline significant association between current HRT use and decreased risk of high-grade DCIS lesions (P = 0.07) in univariate analyses, but this disappeared after adjustment for size and histology. There are important differences between predictors of DCIS and invasive cancer. In contrast to invasive cancer, HRT is not associated with size or grade of DCIS.

Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns.

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Vascular permeability factor (Vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast

Prior studies have indicated that ductal carcinoma in situ (DCIS) lesions are capable of inducing a vascular stroma. However, the mechanisms responsible for angiogenesis in DCIS currently are not defined. The goal of this study was to determine the relationship between the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), and angiogenesis in patients with DCIS. Forty-six breast biopsies with DCIS were characterized with regard to histologic features on hematoxylin and eosin stained sections, and microvessel density and distribution using sections immunostained for factor VIII-related antigen. In addition, in situ hybridization was performed on formalin fixed, paraffin embedded sections using 35S labeled riboprobes specific for VPF/VEGF. VPF/VEGF expression by tumor cells in DCIS was greater than that observed in adjacent benign ductal or lobular epithelial cells in 96% of the evaluable cases. Moreover, the degree of VPF/VEGF mRNA expression was significantly associated with the degree of angiogenesis in these lesions. Among 22 cases with strong VPF/VEGF mRNA expression, the median microvessel count was 100 +/- 30.6 vessels/field. In contrast, among 24 cases with low level VPF/VEGF mRNA expression, the median microvessel count was 71 +/- 48.6 vessels/field (P = 0.04). In addition, high grade DCIS lesions more commonly were associated with strong VPF/VEGF mRNA expression than low grade lesions, but the results were not statistically significant. These findings suggest that VPF/VEGF is an important angiogenic factor in patients with DCIS.