Stefanie Weigel

Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial

PURPOSE We investigated the respective contribution (in terms of cancer yield and stage at diagnosis) of clinical breast examination (CBE), mammography, ultrasound, and quality-assured breast magnetic resonance imaging (MRI), used alone or in different combination, for screening women at elevated risk for breast cancer. METHODS Prospective multicenter observational cohort study. Six hundred eighty-seven asymptomatic women at elevated familial risk (> or = 20% lifetime) underwent 1,679 annual screening rounds consisting of CBE, mammography, ultrasound, and MRI, read independently and in different combinations. In a subgroup of 371 women, additional half-yearly ultrasound and CBE was performed more than 869 screening rounds. Mean and median follow-up was 29.18 and 29.09 months. RESULTS Twenty-seven women were diagnosed with breast cancer: 11 ductal carcinoma in situ (41%) and 16 invasive cancers (59%). Three (11%) of 27 were node positive. All cancers were detected during annual screening; no interval cancer occurred; no cancer was identified during half-yearly ultrasound. The cancer yield of ultrasound (6.0 of 1,000) and mammography (5.4 of 1,000) was equivalent; it increased nonsignificantly (7.7 of 1,000) if both methods were combined. Cancer yield achieved by MRI alone (14.9 of 1,000) was significantly higher; it was not significantly improved by adding mammography (MRI plus mammography: 16.0 of 1,000) and did not change by adding ultrasound (MRI plus ultrasound: 14.9 of 1,000). Positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI. CONCLUSION In women at elevated familial risk, quality-assured MRI screening shifts the distribution of screen-detected breast cancers toward the preinvasive stage. In women undergoing quality-assured MRI annually, neither mammography, nor annual or half-yearly ultrasound or CBE will add to the cancer yield achieved by MRI alone.

Calcifications in Digital Mammographic Screening: Improvement of Early Detection of Invasive Breast Cancers?

PURPOSE To evaluate the relevance of calcifications for invasive breast cancer detection in population-based digital mammographic screening. MATERIALS AND METHODS This study was approved by an independent ethics committee, and no additional informed consent was required. Prospectively documented radiologic cancer features were correlated with pathologic characteristics in 241 breast malignancies diagnosed in 24067 participating women aged 50-69 years (part of the digital German Screening Program; initial screening rate, 92%; detection rate [DR], 1.0%; recall rate [RR], 7.5%). The rates of invasive cancers detected on the basis of calcifications were analyzed against pathologic tumor categories (pT categories) and histologic grades. For comparison of the study data with results of analog screening, data from the literature regarding calcification-specific RR, DR, and positive predictive value for recall (PPV(1)) were calculated. RESULTS The calcification-specific RR was 1.7% (416 of 24067). The calcification-specific DR for invasive cancer was 0.12% (29 of 24067), and the PPV(1) was 7.0% (29 of 416). Of all malignancies detected on the basis of calcification, 38% (29 of 77) were invasive. pT1 cancers showed an inverse association between tumor size and rate of detection on the basis of calcification; differences in rates among pT1 subcategories were statistically significant (P < .001). The proportion of grade 1 pT1 cancers detected on the basis of calcification (eight of 27) did not differ significantly from that of cancers detected on the basis of other radiologic features (46 of 108, P = .24). The calcification-specific invasive cancer DR was significantly higher for digital than for analog mammography. CONCLUSION One-third of malignancies detected on the basis of calcifications only are invasive cancers. They tend to be smaller but not less aggressive than invasive cancers detected on the basis of other features. Compared with published results of analog screening, digital screening offers the potential to increase the rate of invasive cancers detected on the basis of calcifications in population-based mammographic screening.

Thoracic aortic stent graft: comparison of contrast-enhanced MR angiography and CT angiography in the follow-up: initial results

Abstract.The objective of this study was to compare contrast-enhanced magnetic resonance angiography (CE MRA) and multislice computed tomographic angiography (MS CTA) in the follow-up of thoracic stent-graft placement. The CE MRA and MS CTA were performed following nitinol stent-graft treatment due to thoracic aneurysm (n=4), intramural bleeding (n=2) and type-B aortic dissection (n=5). Corresponding evaluation of arterial-phase imaging characteristics focused on the stent-graft morphology and leakage assessment. Stent-graft and aneurysm extensions were comparable between both techniques. Complete exclusion (aneurysm, n=4; dissection, n=2) was assessed with high confidence with CE MRA and MS CTA. Incomplete exclusion (intramural bleeding, n=2; dissection, n=3) was assigned to lower confidence scores on CE MRA compared with MS CTA. On CE MRA the stent-graft lumen demonstrated an inhomogeneous signal, the stent struts could not be assessed. The CE MRA can be used as alternative non-invasive imaging for follow-up of nitinol stent grafts. Arterial-phase leak assessment can be less evident in CE MRA compared with MS CTA studies; therefore, the use of late-phase imaging seems to be necessary. The diagnostic gap of stent-graft fracture evaluation using MRA may be filled with plain radiographs.

Mammography Screening: Evidence, History and Current Practice in Germany and Other European Countries.

In this review, we describe the history, evidence, and current practice of mammography screening in Europe and the newly implemented screening program in Germany. We report results of the first screening rounds in North Rhine-Westphalia and compare these with reference values set by the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis. Finally, we summarize and compare performance indicators of the organized screening program in England, Italy, North Rhine-Westphalia and The Netherlands. Based on results of the first screening rounds, we conclude that the digital mammography screening program in North Rhine-Westphalia performs well and complies with the European guidelines. Besides relatively low attendance rates of approximately 53%, implementation of the German organized breast cancer screening program was successful.

First Epidemiological Analysis of Breast Cancer Incidence and Tumor Characteristics after Implementation of Population-Based Digital Mammography Screening

PURPOSE To epidemiologically evaluate the impact of digital mammography screening on incidence rates and tumor characteristics for breast cancer. MATERIALS AND METHODS The first German digital screening units in the clinical routine were evaluated during the implementation period by using data from the cancer registry to compare the incidence rate of breast cancers and prognostic characteristics. 74 % of women aged 50 - 69 within the region of Muenster/Coesfeld/Warendorf were invited between 10 / 2005 and 12 / 2007 for initial screening; 55 % participated (n = 35 961). RESULTS In 2002 - 2004 the average breast cancer incidence rate (per 100,000) was 297.9. During the implementation of screening, the rate rose to 532.9 in 2007. Of the 349 cancers detected with screening, 76 % (265 / 349) were invasive compared to 90 % (546 / 608) of cases not detected with screening during the same period. 37 % (97 / 265) of cancers detected in the screening program had a diameter of <or= 10 mm and 75 % (198 / 265) were node-negative compared to 15 % (79 / 546) and 64 % (322 / 503), respectively, in cancers detected outside the screening program. The distribution of invasive tumor size (pT categories) and the nodal status differed with statistical significance between cancers detected in and outside the program (p = 0.005 and p = 0.004, respectively). CONCLUSION Epidemiological data shows that the implementation of a population-based screening program led to a relevant increase in the age-specific breast cancer incidence rate. The characteristics of breast cancers detected in the screening program comply with the requirements of the European guidelines and are significantly favorable compared to tumors diagnosed outside the program. These findings indicate that digital mammography screening fulfills the requirements for an early tumor detection tool.

Digital Mammography Screening: Association between Detection Rate and Nuclear Grade of Ductal Carcinoma in Situ

PURPOSE To determine the relationship between overall detection rates of ductal carcinoma in situ (DCIS) and the specific detection rates of low-, intermediate-, and high-grade DCIS at the start of a digital mammography screening program. MATERIALS AND METHODS The study was approved by the local ethics board and did not require informed consent. Data were included of the first round of digital mammography examinations, performed in 17 screening units in women aged 50-69 years from 2005 to 2008. Grading was provided by the cancer registry for 1018 DCIS cases. The association between the overall cancer detection rate (cases per 100 women screened) and the separate cancer detection rate for invasive cancers and for DCIS was assessed. Likewise, the total DCIS cancer detection rate was separated into rates for low, intermediate, and high grades. Spearman rank correlations were used for analysis. RESULTS The overall cancer detection rate correlated with both the cancer detection rate of invasive cancers and the cancer detection rate of DCIS (r = 0.96 and r = 0.88, respectively; P < .001 for both). The cancer detection rate of total DCIS with grading varied among screening units (range, 0.05-0.25), it was borderline not significantly correlated with the cancer detection rate of low-grade DCIS (range, 0.004-0.05; r = 0.49; P = .052), and it showed significant correlations with higher cancer detection rate of intermediate-grade DCIS (range, 0.02-0.12; r = 0.89; P < .001) and of high-grade DCIS (range, 0.03-0.11; r = 0.88; P < .001). CONCLUSION This study demonstrates that high overall cancer detection rates in digital mammography screening are related to high detection rates of invasive cancers, as well as DCIS. Increases in the detection rates of DCIS were not driven by disproportionate increments of the slowly progressive low-grade subtype but rather by increased rates of intermediate- and high-grade subtypes that carry a higher risk of transition to invasive cancers.

Digital Mammography Screening with Photon-counting Technique: Can a High Diagnostic Performance Be Realized at Low Mean Glandular Dose?

PURPOSE To assess screening performance of a direct radiography (DR) photon-counting system versus statewide screening units with different digital technologies. MATERIALS AND METHODS The local ethics board approved retrospective study of prospectively acquired data from the North Rhine-Westphalian mammography screening program (2009-2010). Informed consent was waived. Examinations in 13 312 women with a DR photon-counting system and statewide digital screening examinations in 993 822 women were included (37 computed radiography mammography systems and 55 DR systems). Diagnostic performance was assessed with cancer detection rate, recall rate, and proportion of small invasive cancers and ductal carcinoma in situ (DCIS). Mean glandular dose was calculated for DR photon counting and for a conventional DR subgroup. Differences were tested with χ(2) and t tests (P < .05). RESULTS The cancer detection rate for subsequent screenings was higher for DR photon counting than statewide rates (0.76% [67 of 8842] vs 0.59% [3108 of 527 194], P = .05) at a higher recall rate (5.4% [475 of 8842] vs 3.3% [17 656 of 527 194], P = .001). Detection of invasive cancers up to 10 mm for DR photon counting was high for initial (40% [14 of 35]) and subsequent (42% [19 of 45]) screenings but not significantly different from statewide rates (initial, 31.6% [942 of 2979], P = .50; subsequent, 32.5% [765 of 2353], P = .25). The DCIS subsequent screening rate was higher for DR photon counting than statewide screening (0.23% [20 of 8842] vs 0.12% [616 of 527 194], P = .01) and the conventional DR subgroup (0.23% [20 of 8842] vs 0.12% [65 of 52 813], P = .025). Mean glandular dose for DR photon counting was significantly lower than that for conventional DR (0.60 mGy ± 0.20 vs 1.67 mGy ± 0.47 [craniocaudal views], 0.64 mGy ± 0.23 vs 1.79 mGy ± 0.53 [mediolateral oblique views], both P = .0001). CONCLUSION Digital mammography screening with dose-efficient photon counting enables desirable detection rates of small invasive cancers and DCIS. Higher detection rates compared with statewide performance occurred with subsequent screening but had higher recall rates.

Digital Mammography Screening: Does Age Influence the Detection Rates of Low-, Intermediate-, and High-Grade Ductal Carcinoma in Situ?

PURPOSE To investigate the association between age at screening and detection rates for ductal carcinoma in situ (DCIS) separately for different nuclear grades after introduction of a population-based digital mammography screening program. MATERIALS AND METHODS The retrospective study was approved by the ethics board and did not require informed consent. In 733 905 women aged 50-69 years who participated in a screening program for the first time in 2005-2008 (baseline examinations were performed with digital mammography), DCIS detection rates were determined for 5-year age groups (detection rates per 1000 women screened) to distinguish high-, intermediate-, and low-grade DCIS. Multivariable logistic regression was used to compare detection rates between age groups by adjusting for screening units (P < .05). RESULTS There were 989 graded DCIS diagnoses among 733 905 women (detection rate, 1.35‰): 419 diagnoses of high-grade DCIS (detection rate, 0.57‰), 388 diagnoses of intermediate-grade DCIS (detection rate, 0.53‰), and 182 diagnoses of low-grade DCIS (detection rate, 0.25‰). Detection rate for types of DCIS combined increased significantly across age groups (50-54 years, detection rate of 1.15‰ [254 of 220 985 women]; 55-59 years, detection rate of 1.23‰ [218 of 177 782 women]; 60-64 years, detection rate of 1.34‰ [201 of 150 415 women]; and 65-69 years, detection rate of 1.71‰ [316 of 184 723 women]; P < .001). Of note, the detection rate for high-grade DCIS showed a significant increase with age (odds ratio, 1.18 per 5-year age group; P < .0001). The increase was lower for intermediate-grade DCIS (odds ratio, 1.11; P = .016) and not significant for low-grade DCIS (P = .10). CONCLUSION Total DCIS detection rates increase with age, mostly because of an increase in high- and intermediate-grade DCIS, which are precursor lesions that carry a higher risk for transition to more aggressive invasive breast cancer than low-grade DCIS.

Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening

PURPOSE The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. MATERIALS AND METHODS The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). RESULTS The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). CONCLUSION During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. KEY POINTS • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a significant effect of screening on the 2-year incidence of advanced stages, predominately in the age group 60 to 69 years.

Rates of Presurgical Underestimation of Breast Cancer after Standardized Assessment of Breast Calcifications

PURPOSE To determine the frequency of histopathological underestimation of breast cancer after vacuum-assisted biopsy (VAB) in standardized assessment of breast calcifications compared to postsurgical diagnosis. MATERIALS AND METHODS The retrospective study included acquired data of 506 consecutively examined women, who underwent VAB for the assessment of pure calcifications after standardized digital mammographic and sonographic imaging. 119/506 (24.5 %) women underwent further surgical procedures: 37 women had a surgical diagnostic excision biopsy, 82 women a surgical procedure based on a therapeutic concept. Presurgical results of VAB were compared with the postsurgical histopathological reports. RESULTS In 91/119 women (76.5 %) the final histology was malignant. The rate of ductal carcinoma in situ (DCIS) was 79.1 % (72/91) and the rate of invasive carcinoma was 20.9 % (19/91). In 9/37 women with diagnostic excision biopsy, the presurgical status of benign or uncertain changed to a postsurgical diagnosis of malignant (24.3 %). In eight cases underestimation included DCIS (21.6 %) and in one case invasive cancer (2.7 %). Seven of the nine underestimated cases (77.8 %) resulted from excision biopsy of atypical epithelial proliferation of ductal type (AEPDT, positive predictive value 30.4 % (7/23)). After surgery due to DCIS in 7/71 women invasive breast cancer was diagnosed (9.9 %). In 11/82 women with oncological surgery, invasive cancer was already diagnosed by VAB. CONCLUSION Underestimation of invasive cancer in terms of presurgical DCIS diagnosis can be minimized by the standardized assessment protocol to about 10 %. Underestimation of DCIS is mainly related to presurgical diagnosis of AEPDT. KEY POINTS • The standardized use of digital mammographic and sonographic imaging prior to vacuum-assisted biopsy is suitable for minimizing underestimation of invasive breast cancer. AEPDT represents a high risk diagnosis for underestimation of DCIS.