Heribert Bieling

MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study

BACKGROUND Diagnosing breast cancer in its intraductal stage might be helpful to prevent the development of invasive cancer. Our aim was to investigate the sensitivity with which ductal carcinoma in situ (DCIS) is diagnosed by mammography and by breast MRI. METHODS During a 5-year period, 7319 women who were referred to an academic national breast centre received MRI in addition to mammography for diagnostic assessment and screening. Mammograms and breast MRI studies were assessed independently by different radiologists. We investigated the sensitivity of each method of detection and compared the biological profiles of mammography-diagnosed DCIS versus DCIS detected by MRI alone. We also compared the risk profiles of women with mammography-detected DCIS with those of MRI-detected DCIS. FINDINGS 193 women received a final surgical pathology diagnosis of pure DCIS. Of those, 167 had undergone both imaging tests preoperatively. 93 (56%) of these cases were diagnosed by mammography and 153 (92%) by MRI (p<0.0001). Of the 89 high-grade DCIS, 43 (48%) were missed by mammography, but diagnosed by MRI alone; all 43 cases missed by mammography were detected by MRI. By contrast, MRI detected 87 (98%) of these lesions; the two cases missed by MRI were detected by mammography. Age, menopausal status, personal or family history of breast cancer or of benign breast disease, and breast density of women with MRI-only diagnosed DCIS did not differ significantly from those of women with mammography-diagnosed DCIS. INTERPRETATION MRI could help improve the ability to diagnose DCIS, especially DCIS with high nuclear grade.

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.

Abbreviated Breast Magnetic Resonance Imaging (MRI): First Postcontrast Subtracted Images and Maximum-Intensity Projection-A Novel Approach to Breast Cancer Screening With MRI

PURPOSE We investigated whether an abbreviated protocol (AP), consisting of only one pre- and one postcontrast acquisition and their derived images (first postcontrast subtracted [FAST] and maximum-intensity projection [MIP] images), was suitable for breast magnetic resonance imaging (MRI) screening. METHODS We conducted a prospective observational reader study in 443 women at mildly to moderately increased risk who underwent 606 screening MRIs. Eligible women had normal or benign digital mammograms and, for those with heterogeneously dense or extremely dense breasts (n = 427), normal or benign ultrasounds. Expert radiologists reviewed the MIP image first to search for significant enhancement and then reviewed the complete AP (consisting of MIP and FAST images and optionally their nonsubtracted source images) to characterize enhancement and establish a diagnosis. Only thereafter was the regular full diagnostic protocol (FDP) analyzed. RESULTS MRI acquisition time for FDP was 17 minutes, versus 3 minutes for the AP. Average time to read the single MIP and complete AP was 2.8 and 28 seconds, respectively. Eleven breast cancers (four ductal carcinomas in situ and seven invasive cancers; all T1N0 intermediate or high grade) were diagnosed, for an additional cancer yield of 18.2 per 1,000. MIP readings were positive in 10 (90.9%) of 11 cancers and allowed establishment of the absence of breast cancer, with a negative predictive value (NPV) of 99.8% (418 of 419). Interpretation of the complete AP, as with the FDP, allowed diagnosis of all cancers (11 [100%] of 11). Specificity and positive predictive value (PPV) of AP versus FDP were equivalent (94.3% v 93.9% and 24.4% v 23.4%, respectively). CONCLUSION An MRI acquisition time of 3 minutes and an expert radiologist MIP image reading time of 3 seconds are sufficient to establish the absence of breast cancer, with an NPV of 99.8%. With a reading time < 30 seconds for the complete AP, diagnostic accuracy was equivalent to that of the FDP and resulted in an additional cancer yield of 18.2 per 1,000.

Supplemental Breast MR Imaging Screening of Women with Average Risk of Breast Cancer

Purpose To investigate the utility and accuracy of breast magnetic resonance (MR) imaging as a supplemental screening tool in women at average risk for breast cancer and to investigate the types of cancer detected with MR imaging screening. Materials and Methods This prospective observational study was conducted at two academic breast centers in women aged 40-70 years without breast cancer-associated risk factors (lifetime risk <15%). Between January 2005 and December 2013, women with at least minimal residual breast tissue (American College of Radiology categories A-D) and normal conventional imaging findings (screening mammography with or without screening ultrasonography [US]) were invited to undergo supplemental MR imaging screening. Outcome measures were supplemental cancer detection rates, interval cancer rates, and biologic profiles of MR imaging-detected additional cancers, as well as specificity and positive predictive value (PPV) of MR imaging screening. Tissue diagnoses or 2 years of follow-up were used to establish the reference standard. Results A total of 2120 women were recruited and underwent 3861 screening MR imaging studies, covering an observation period of 7007 women-years. Breast MR imaging depicted 60 additional breast cancers (ductal carcinoma in situ, n = 20; invasive carcinoma, n = 40) for an overall supplemental cancer detection rate of 15.5 per 1000 cases (95% confidence interval [CI]: 11.9, 20.0). Forty-eight additional cancers were detected with MR imaging at initial screening (supplemental cancer detection rate, 22.6 per 1000 cases). During the 1741 subsequent screening rounds, 12 of 13 incident cancers were found with MR imaging alone (supplemental cancer detection rate, 6.9 per 1000 cases). One cancer was diagnosed with all three methods (mammography, US, and MR imaging), and none were diagnosed with mammography only or US only. Cancers diagnosed with MR imaging were small (median, 8 mm), node negative in 93.4% of cases, and dedifferentiated (high-grade cancer) in 41.7% of cases at prevalence screening and 46.0% of cases at incidence screening. No interval cancers were observed. MR imaging screening offered high specificity (97.1%; 95% CI: 96.5, 97.6) and high PPV (35.7%; 95% CI: 28.9, 43.1). Conclusion In women at average risk for breast cancer, MR imaging screening improves early diagnosis of prognostically relevant breast cancer.

Impact of Preoperative Breast MR Imaging and MR-guided Surgery on Diagnosis and Surgical Outcome of Women with Invasive Breast Cancer with and without DCIS Component

Purpose To (a) compare the diagnostic accuracy of breast magnetic resonance (MR) imaging with that of conventional imaging (digital mammography and breast ultrasonography) in the identification of ductal carcinoma in situ (DCIS) components of biopsy-proven invasive breast cancer before surgery and (b) investigate the surgical outcome (positive margin rates and mastectomy rates) of women with breast cancer who underwent preoperative MR imaging combined with MR-guided needle biopsy and/or MR-guided lesion localization or bracketing where appropriate. Materials and Methods The authors performed a prospective two-center study of 593 consecutive patients with biopsy-proven invasive breast cancer who underwent breast MR imaging in addition to conventional imaging. MR-guided vacuum biopsy and MR-guided lesion bracketing were performed for DCIS components visible at MR imaging alone. The accuracy of breast MR imaging was compared with that of conventional imaging, and surgical outcomes (positive margin and mastectomy rates) were investigated. Results Surgical-pathologic assessment demonstrated DCIS components in 139 of the 593 women (23.4%). The sensitivity of MR imaging for the diagnosis of DCIS components pre-operatively (84.9%; 118 of 139) was significantly higher than that of conventional imaging (36.7%; 51 of 139) (P < .0001); more than half of DCIS components (51.1%; 71 of 139) were detected only with MR imaging. The sensitivity advantage of MR imaging over conventional imaging increased with increasing relative size of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for small, marginal DCIS components was 56.8% (21 of 37) versus 29.7% (11 of 37); the sensitivity for extensive DCIS components was 91.7% (55 of 60) versus 41.7% (25 of 60); the sensitivity for large, predominant DCIS components was 100.0% (42 of 42) versus 35.7% (15 of 42). Moreover, the sensitivity advantage of MR imaging over conventional imaging increased with increasing nuclear grade of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for low-grade DCIS components was 74.0% (20 of 27) versus 40.7% (11 of 27); the sensitivity for intermediate-grade DCIS components was 84.1% (53 of 63) versus 34.9% (22 of 63); the sensitivity for high-grade DCIS components was 91.8% (45 of 49) versus 36.7% (18 of 49) (P < .05-.001 for all). Positive margin rates were low overall (3.7% [95% Clopper Pearson confidence interval [CI]: 2.3%, 5.6%]) and did not differ significantly between the 139 women with DCIS components (5.0% [95% CI: 2.0%, 10.1%]) compared with the 454 women without such components (3.3% [95% CI: 1.9%, 5.4%]). The same was true for mastectomy rates (10.8% [95% CI: 6.2%, 17.2%] vs 8.1% [95% CI: 5.8%, 11.1%]). Conclusion Breast MR imaging improves depiction of DCIS components of invasive breast cancers before surgery and is associated with positive margin and mastectomy rates that are low irrespective of the presence or absence of DCIS components.

Breast MRI screening of women at average risk of breast cancer: An observational cohort study.

1 Background: Breast-MRI is currently recommended for screening women at high-risk of breast-cancer only. However, despite decades of mammographic-screening, breast-cancer continues to represent a major cause of cancer-death also for women at average-risk - suggesting a need for improved methods for early diagnosis also for these women. Therefore, we investigated the utility of supplemental MRI-screening of women who carry an average-risk of breast-cancer. METHODS Prospective observational cohort-study conducted in two academic breast-centers on asymptomatic women at average-risk in the usual age range for screening-mammography (40 to 70). Women underwent DCE-breast-MRI in addition to mammography every 12, 24, or 36 months, plus follow-up of 2 years to establish a standard-of-reference. We report on the supplemental-cancer-yield, interval-cancer-rate, diagnostic accuracy of screening-MRI, and biologic profiles of additional, MRI-detected breast-cancers. RESULTS 2120 women underwent a total 3861 MRI-studies covering 7007 women-years. Breast-cancer was diagnosed in 61/2120 women (DCIS: 20, invasive: 41), and ADH/LIN in another 21. Interval-cancer-rate was 0%, irrespective of screening interval. Forty-eight women were diagnosed with breast-cancer at prevalence-screening by MRI alone (supplemental cancer-detection-rate: 22.6 per 1000); 13 women were diagnosed with breast-cancer in 1741 incidence-screening-rounds collected over 4887 women-years. A total 12 of these 13 incident cancers were diagnosed by screening-MRI alone (supplemental-cancer-detection-rate: 6.9 per 1000), one by MRI and mammography, none by mammography alone. Supplemental-cancer-detection-rate was independent of mammographic breast-density. Invasive cancers were small (mean size: 8mm), node-negative in 93.4%, ER/PR-negative in 32.8%, and de-differentiated in 41.7% at prevalence, and 46.0% at incidence-screening. Specificity of MRI-screening was 97.1%, False-Positive-Rate 2.9%. CONCLUSIONS MRI-screening improves detection of biologically relevant breast-cancer in women at average-risk, and reduces the interval-cancer-rate down to 0%, at a low false-positive rate.

Accelerated breast MRI for breast cancer screening.

1 Background: Current breast MRI protocols are designed for diagnostic, not for screening purposes, and are therefore time consuming to acquire and to read. We investigated whether an abridged breast MRI protocol, consisting only of the first post contrast subtracted (FAST) images and their maximum intensity projection (MIP), would be suitable for screening purposes. Idea was to trade some of the very high sensitivity of breast MRI for acquisition and interpretation speed. Long term goal is to increase the access to breast MRI by reducing the cost associated with the examination. METHODS 443 women at increased risk of breast cancer, with negative digital mammography, underwent 606 breast MRI screening studies. Images were prospectively read by experienced breast radiologists. Readers were asked to first review the MIPs and search for significant enhancement, then to evaluate the FAST images for possible further categorization of enhancement, and only thereafter, to analyse the full diagnostic breast MRI protocol. We compared diagnostic yield and accuracy of MIP and of FAST readings vs. that of the full protocol. RESULTS MR table time for the full protocol was 21 minutes, table time for FAST images and MIPs was under 3 minutes. Average time to read MIP and FAST image was 2.8 seconds and 28 seconds, respectively. A total 11 breast cancers (4 DCIS, 7 invasive, median size 8 mm, all intermediate or high grade), were diagnosed in the 603 examinations for an additional cancer yield of 18.2/1000. MIPs were positive in 9/11 (82%); FAST readings as well as the full protocol were positive in 10/11 (91%). NPV of the MIP and FAST readings was 99.6% (484/486) and 99.8%, respectively. Specificity of FAST readings was equivalent to that of the full protocol (94.4%), with 33 vs. 35 false-positive diagnoses. CONCLUSIONS In this high risk screening cohort, an MR table time of 3 minutes and an expert radiologist reading time of 2 seconds for the interpretation of the MIP image was sufficient to establish absence of breast cancer with a negative predictive value of 99.6%. With the same abridged MR protocol and an expert reading time of under 30 seconds for interpretation of FAST images, sensitivity and specificity was identical to that of the full protocol, allowing an additional cancer yield of 18.2/1,000.

Target lesion selection: an important factor causing variability of response classification in the Response Evaluation Criteria for Solid Tumors 1.1.

PurposeWe conducted a systematic analysis of factors (manual vs automated and unidimensional vs 3-dimensional size assessment, and impact of different target lesion selection) contributing to variability of response categorization in the Response Evaluation Criteria for Solid Tumors 1.1. Patients and MethodsA total of 41 female patients (58.1 ± 13.2 years old) with metastatic breast cancer underwent contrast-enhanced thoracoabdominal computed tomography for initial staging and first follow-up after systemic chemotherapy. Data were independently interpreted by 3 radiologists with 5 to 9 years of experience. In addition, response was evaluated by a computer-assisted diagnosis system that allowed automated unidimensional and 3-dimensional assessment of target lesions. ResultsOverall, between-reader agreement was moderate (&kgr; = 0.53), with diverging response classification observed in 19 of 41 patients (46%). In 25 patients, readers had chosen the same, and in 16, readers had chosen different target lesions. Selection of the same target lesions was associated with a 76% rate of agreement (19/25) with regard to response classification; selection of different target lesions was associated with an 81% rate of disagreement (13/16) (P < 0.001). After dichotomizing response classes according to their therapeutic implication in progressive versus nonprogressive, disagreement was observed in 11 of 41 patients (27%) (&kgr; = 0.57). In 9 of these 11 patients, readers had chosen different target lesions. Disagreement rates due to manual versus automated or unidimensional versus volumetric size measurements were less important (11/41 and 6/41; 27% and 15%, respectively). ConclusionsA major source of variability is not the manual or unidimensional measurement, but the variable choice of target lesions between readers. Computer-assisted diagnosis–based analysis or tumor volumetry can help avoid variability due to manual or unidimensional measurements only but will not solve the problem of target lesion selection.

Preoperative breast MRI and MR-guided surgery of invasive breast cancers with and without DCIS components.

58 Background: DCIS-components of invasive breast-cancers are a major cause for positive margins and reoperations in women undergoing breast-conserving-surgery. We investigated whether breast-MRI, through improved diagnosis of such DCIS-components, combined with MR-guided needle biopsy and pre-operative MR-guided lesion bracketing where appropriate, would help reduce reoperation-rates for invasive breast cancers. Our hypothesis was that with improved diagnosis of local disease extent through MRI and MR-guided surgery, reoperation rates should be low, and should be independent of the presence or absence of a DCIS-component. METHODS Prospective study in two academic breast-centers on consecutive patients with newly-diagnosed invasive breast-cancer. Women underwent breast-MRI in addition to conventional imaging (CI; digital-mammography/breast-ultrasound), and MR-guided needle-biopsy and preoperative MR-guided lesion bracketing where appropriate. Accuracy of breast-MRI for diagnosing DCIS-components was compared with that of CI, stratified by nuclear-grade and relative size of DCIS-components. Surgical outcomes (reoperation and mastectomy-rates) were recorded, stratified by presence or absence of DCIS-components. RESULTS 593 women were included. Surgical-pathology documented DCIS-components in 139/593 (23.4%) women. Sensitivity of MRI (84.9%) for demonstrating DCIS-components was significantly higher than that of CI (36.7%) (p < 0.0001); over half (51.1%) of DCIS-components were only detected by MRI. The sensitivity advantage of MRI over CI increased significantly with increasing relative size and nuclear-grade of the DCIS-component. Reoperation-rates were equivalent for women with vs. without DCIS-components (10.1% vs. 9.9%); mastectomy rates were 10.8% and 8.1%, respectively. Similar Positive-Predictive-Values were achieved with CI and MRI. CONCLUSIONS Breast-MRI significantly improves depiction of DCIS-components of invasive breast-cancers prior to surgery. Use of breast-MRI and MR-guided surgery translates into low reoperation rates for women with operable invasive breast-cancer, which were similar for women with or without DCIS-components.