Kevin Strobel

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.

Assessment of BI-RADS Category 4 Lesions Detected with Screening Mammography and Screening US: Utility of MR Imaging

PURPOSE To investigate the utility of magnetic resonance (MR) imaging according to different types of Breast Imaging Reporting and Data System (BI-RADS) category 4 findings from screening mammography and/or screening ultrasonography (US). MATERIALS AND METHODS This institutional review board-approved prospective study included 340 patients in whom 353 lesions were detected at screening mammography or US and were rated BI-RADS category 4 after appropriate conventional work-up. Written informed consent was obtained from all patients. Women underwent standard dynamic contrast material-enhanced MR imaging for further assessment. Women with negative or benign MR findings who did not proceed to biopsy underwent intensified follow-up for at least 18 months. Pure clustered microcalcifications were followed up for at least 24 months. RESULTS Of the 353 study findings, 66 (18.7%) were finally shown to be true-positive (23 cases of ductal carcinoma in situ [DCIS], 43 invasive cancers) and 287 (81.3%) were false-positive. Assessment of MR imaging findings led to a correct diagnosis of no breast cancer in 264 of the 287 false-positive findings (92%) and helped confirm the presence of breast cancer in 63 of 66 malignancies. The false-negative rate for pure clustered microcalcifications was 12% (three of 25 cases) because of three nonenhancing low-grade DCIS cases; in turn, MR imaging depicted additional invasive cancers in three women with false-positive findings from mammography and US. For mammographic findings other than pure clustered microcalcifications, MR imaging increased the positive predictive value (PPV) from 17.5% (21 of 120 cases; 95% confidence interval [CI]: 10.7%, 24.3%) to 78% (21 of 27 cases; 95% CI: 62.1%, 93.5%), with a false-negative rate of 0%. For all US findings, MR imaging increased the PPV from 12.9% (20 of 155 cases; 95% CI: 7.6%, 18.2%) to 69% (20 of 29 cases; 95% CI: 52.2%, 85.8%), again with a false-negative rate of 0%. MR imaging resulted in false-positive findings that led to MR imaging-guided biopsy in five of the 340 patients (1.5%). CONCLUSION MR imaging is useful for the noninvasive work-up of lesions classified as BI-RADS category 4 at mammography or US and can help avoid 92% of unnecessary biopsies. The false-negative rate was 0% for all US findings and for all mammographic findings except pure clustered microcalcifications. Additional invasive cancers were identified in three women with false-positive findings from mammography and US.

Does MRI Breast “Density” (Degree of Background Enhancement) Correlate With Mammographic Breast Density?

To investigate whether mammographic breast densities and the respective degree of MRI background enhancement would correlate. Mammographic breast density is coded to communicate how likely a cancer is obscured by parenchyma. Similarly, background enhancement in breast MRI could obscure enhancing cancer tissue.

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.

Safety and Efficacy of Magnetic Resonance-Guided Vacuum-Assisted Large-Volume Breast Biopsy (MR-Guided VALB).

Objective Magnetic resonance (MR)-guided vacuum-biopsy is technically demanding and may fail depending on target-lesion size or breast size, and location of lesions within the breast. We developed an MR-guided vacuum-assisted biopsy protocol that collects larger amounts of tissue, aiming at an at least partial or complete ablation of the target-lesion, just as it is intended during surgical (excisional) biopsy. Rationale is to avoid biopsy failures (false-negative results due to undersampling) by collecting larger amounts of tissue. We report on our experience with MR-guided vacuum-assisted large-volume breast biopsy (VALB) (MR-guided VALB) with regard to clinical success and complication rates. Materials Institutional review board–approved analysis of 865 patients with 1414 MR imaging (MRI)-only breast lesions who underwent tissue sampling under MRI guidance. Magnetic resonance–guided VALB was performed on a 1.5 T-system with a 9G system. Per target lesion, we collected at least 24 samples, with the biopsy notch directed toward the position of the target until on postbiopsy control imaging the target lesion appeared completely or at least greatly removed. The standard-of-reference was established by at least 24-months follow-up (for benign biopsy results), or results of surgical histology (for malignant or borderline results). We investigated the technical success rates as a function of factors that usually interfere with MR-guided vacuum biopsy. Results Target lesions were located in the central versus peripheral parts of the breast in 66.6% (941/1414) versus 33.6% (473/1414), occurred in large, intermediate, or small breasts in 22.7% (321/1414), 56.4% (797/1414), or 20.9% (296/1414), corresponded to nonmass enhancement (NME) versus mass enhancement (ME) in 64.0% (905/1414) vs. 36.0% (509/1414), with an average size of 23 mm for NME versus 9 mm for ME, respectively. Primary technical failures, that is, inability to reach the target lesion occurred in 0.2% of patients (2/865) and 0.1% of target lesions (2/1414). Successful biopsy, that is, an MR-guided VALB diagnosis matching with the standard of reference, was achieved in 99.5% (859/863) of patients and 99.7% (1408/1412) target lesions that had been amenable to MR-guided VALB. In 0.5% of patients (4/863) and 0.3% of target lesions (4/1412), a radiologic-pathologic mismatch suggested a false-negative biopsy, confirmed by secondary excisional biopsy. The likelihood of failure was independent of the lesions location in the breast, breast size, target lesion size, or target lesion type (NME vs ME). None of the patients with benign MR-guided VALB diagnoses developed breast cancer at the biopsy site during follow-up of 2 years. None of the patients developed major complications. Conclusion Magnetic resonance–guided VALB is a safe procedure that is associated with a high success rate (99.7%) that is independent of the size, type, or location of a target lesion, or the size of the breast, and is associated with a very low complication rate.

Abstract S1-09: MRI screening of women at average risk of breast cancer

Background: In asymptomatic women at average risk, screening mammography, possibly amended by breast ultrasound is recommended for early detection of breast cancer. Breast MRI is established for screening women at high familial risk, but there are no data available to support its use in women at average risk. Therefore, we systematically offered dynamic contrast enhanced breast MRI to asymptomatic women at average risk who had normal screening mammograms and (in dense breasts) normal screening ultrasound, in order to investigate the added cancer yield and accuracy of breast MRI in the average-risk screening situation. Methods: Between January 2005 and December 2010, 1387 women at average risk of breast cancer, i.e. without personal or family history of breast or ovarian cancer, or tissue diagnosis of proliferative changes or atypias underwent a total of 1705 annual breast MRI screening studies at our institution. Mean age was 54 years, range 42-71 years, median 56. All women had normal clinical breast examinations and normal (BI-RADS 1-2) digital screening mammograms performed in accordance with EU guidelines. In women with breast densites beyond ACR II additional high frequency (> 10 MHz) physician-performed breast ultrasound was performed and women were included only if this breast ultrasound was normal. Patients underwent bilateral DCE breast MRI at 1.5T using a 2D GE pulse sequence. MRI studies were interpreted by two experienced breast radiologist in consensus. All suspicious lesions detected by MRI alone were clarified by MR guided vacuum assisted breast biopsy. Results: A total of 54 MRIs were rated positive (MR-BI-RADS 4/5) (54/1705; 3.2%). Biopsies performed in these women were positive for breast cancer or DCIS in 18, and revealed high risk lesions in another 8 patients, yielding an additional cancer yield of 11/1000. In 28 women, biopsy revealed benign changes only. This translates into a PPV of 33% (18/54), or 48% (26/54) if high risk lesions are included. Of the 18 cancers, 11 (61%) were invasive and 7 (39%) DCIS. Mean size of invasive cancers was 11 mm (median 10, range 4 -22). Invasive cancers were intermediate or high grade in 9/11, DCIS in 6/7. All invasive cancers were staged pN0, M0. Minimal cancer rate was 13/18 (72%). Distribution of mammographic breast densities in women with MRI-diagnosed cancer was as follows: ACR I in 2 (11%), ACR II in 3 (17%), ACR III in 8 (44%), ACR IV in 5 (28%). This was equivalent to the distribution of breast densities in the entire cohort. Conclusions: In this cohort of heavily pre-screened women at average risk, the additional cancer yield achieved through MRI was high (11/1000). Although the biologic profile of MRI-only detected additional cancers was indicative of prognostically relevant disease, with a high proportion of high-grade cancers, stage distribution of cancers was favorable. In experienced hands, the PPV of MRI screening in this average risk cohort was comparable to those of mammographic screening programs or to that of MRI high risk screening cohorts. Mammographic breast density did not predict the likelihood with which additional cancers were identified through MRI. In women with dense breasts who underwent screening US in addition to mammography, there is still a significant reservoir of undetected cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S1-09.

Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening

BackgroundBreast magnetic resonance imaging (MRI) has been reported to frequently result in false-positive diagnoses, limiting its positive predictive value (PPV). However, for PPV calculation, all nonmalignant tissue changes are equally considered false-positive, although the respective prognostic importance, and thus patient management implications, of different pathologies may well differ. We investigated the pathology of false-positive diagnoses made by MRI compared with radiographic (digital mammography/tomosynthesis [DM/DBT]) screening.MethodsWe conducted an institutional review board-approved prospective analysis of 710 consecutive asymptomatic women at average risk for breast cancer who underwent vacuum biopsy with or without surgical biopsy for screen-detected DM/DBT (n = 344) or MRI (n = 366) findings. We compared the frequency of false-positive biopsies (given by PPV3), as well as the types of nonmalignant tissue changes that caused the respective false-positive biopsies. In an order of increasing relative risk of subsequent breast cancer, pathologies of false-positive biopsies were categorized as nonproliferative, simple proliferative, complex proliferative, or atypical proliferative (including lobular carcinoma in situ/lobular intraepithelial neoplasia). The Mann-Whitney U test was used to compare distributions.ResultsHistology yielded nonmalignant tissue in 202 of 366 biopsies done for positive MRI studies and 195 of 344 biopsies for positive DM/DBT studies, respectively, yielding a similar PPV3 percentages of 44.8% (164 of 202) and 43.3% (149 of 202) for both methods. However, the distribution of tissue types that caused false-positive diagnoses differed significantly (p < 0.0001). On the basis of MRI, high-risk atypical proliferative changes (40.1%; 81 of 202) were most common, followed by complex proliferative changes (23.8%; 48 of 202). In DM/DBT, low-risk, nonproliferative changes were the dominant reason for false-positive diagnoses (49.7%; 97 of 195), followed by simple proliferative changes (25.2%; 51 of 195). Low-risk nonproliferative changes resulted in false-positive diagnoses based on MRI as infrequently as did high-risk atypical proliferative changes based on DM/DBT (18.8% [38 of 202] vs. 18.0% [35 of 195]). The likelihood of a false-positive diagnosis including atypias was twice as high in women undergoing biopsy for MRI findings (81 of 202; 40%) as for those with DM/DBT findings (35 of 195; 18%).ConclusionsThe prognostic importance, and thus the clinical implications, of false-positive diagnoses made on the basis of breast MRI vs. radiographic screening differed significantly, with a reversed prevalence of high- and low-risk lesions. This should be taken into account when discussing the rate of false-positive diagnoses (i.e., PPV levels of MRI vs. radiographic screening). Current benchmarks that rate the utility of breast cancer screening programs (i.e., cancer detection rates and PPVs) do not reflect these substantial biological differences and the different prognostic implications.