Lars J. Grimm

Benefits and Harms of Breast Cancer Screening A Systematic Review

IMPORTANCE Patients need to consider both benefits and harms of breast cancer screening. OBJECTIVE To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy. EVIDENCE REVIEW We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews. FINDINGS Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE. CONCLUSIONS AND RELEVANCE For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Radiogenomic Analysis of Breast Cancer: Luminal B Molecular Subtype Is Associated with Enhancement Dynamics at MR Imaging

PURPOSE To investigate associations between breast cancer molecular subtype and semiautomatically extracted magnetic resonance (MR) imaging features. MATERIALS AND METHODS Imaging and genomic data from the Cancer Genome Atlas and the Cancer Imaging Archive for 48 patients with breast cancer from four institutions in the United States were used in this institutional review board approval-exempt study. Computer vision algorithms were applied to extract 23 imaging features from lesions indicated by a breast radiologist on MR images. Morphologic, textural, and dynamic features were extracted. Molecular subtype was determined on the basis of genomic analysis. Associations between the imaging features and molecular subtype were evaluated by using logistic regression and likelihood ratio tests. The analysis controlled for the age of the patients, their menopausal status, and the orientation of the MR images (sagittal vs axial). RESULTS There is an association (P = .0015) between the luminal B subtype and a dynamic contrast material-enhancement feature that quantifies the relationship between lesion enhancement and background parenchymal enhancement. Cancers with a higher ratio of lesion enhancement rate to background parenchymal enhancement rate are more likely to be luminal B subtype. CONCLUSION The luminal B subtype of breast cancer is associated with MR imaging features that relate the enhancement dynamics of the tumor and the background parenchyma.

Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms.

To identify associations between semiautomatically extracted MRI features and breast cancer molecular subtypes.

Abbreviated Screening Protocol for Breast MRI: A Feasibility Study

RATIONALE AND OBJECTIVES To compare the performance of two shortened breast magnetic resonance imaging (MRI) protocols to a standard MRI protocol for breast cancer screening. MATERIALS AND METHODS In this Health Insurance Portability and Accountability Act compliant, institutional review board-approved pilot study, three fellowship-trained breast imagers evaluated 48 breast MRIs (24 normal, 12 benign, and 12 malignant) selected from a high-risk screening population. MRIs were presented in three viewing protocols, and a final Breast Imaging-Reporting and Data System assessment was recorded for each case. The first shortened protocol (abbreviated 1) included only fat-saturated precontrast T2-weighted, precontrast T1-weighted, and first pass T1-weighted postcontrast sequences. The second shortened protocol (abbreviated 2) included the abbreviated 1 protocol plus the second pass T1-weighted postcontrast sequence. The third protocol (full), reviewed after a 1-month waiting period, included a nonfat-saturated T1-weighted sequence, fat-saturated T2-weighted, precontrast T1-weighted, and three or four dynamic postcontrast sequences. Interpretation times were recorded for the abbreviated 1 and full protocols. Sensitivity and specificity were compared via a chi-squared analysis. This pilot study was designed to detect a 10% difference in sensitivity with a power of 0.8. RESULTS There was no significant difference in sensitivity between the abbreviated 1 (86%; P = .22) or abbreviated 2 (89%; P = .38) protocols and the full protocol (95%). There was no significant difference in specificity between the abbreviated 1 (52%; P = 1) or abbreviated 2 (45%; P = .34) protocols and the full protocol (52%). The abbreviated 1 and full protocol interpretation times were similar (2.98 vs. 3.56 minutes). CONCLUSIONS In this pilot study, reader performance comparing two shortened breast MRI protocols to a standard protocol in a screening cohort were similar, suggesting that a shortened breast MRI protocol may be clinically useful, warranting further investigation.

Can Breast Cancer Molecular Subtype Help to Select Patients for Preoperative MR Imaging

PURPOSE To assess whether breast cancer molecular subtype classified by surrogate markers can be used to predict the extent of clinically relevant disease with preoperative breast magnetic resonance (MR) imaging. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved study, informed consent was waived. Preoperative breast MR imaging reports from 441 patients were reviewed for multicentric and/or multifocal disease, lymph node involvement, skin and/or nipple invasion, chest wall and/or pectoralis muscle invasion, or contralateral disease. Pathologic reports were reviewed to confirm the MR imaging findings and for hormone receptors (estrogen and progesterone subtypes), human epidermal growth factor receptor type 2 (HER2 subtype), tumor size, and tumor grade. Surrogates were used to categorize tumors by molecular subtype: hormone receptor positive and HER2 negative (luminal A subtype); hormone receptor positive and HER2 positive (luminal B subtype); hormone receptor negative and HER2 positive (HER2 subtype); hormone receptor negative and HER2 negative (basal subtype). All patients included in the study had a histologic correlation with MR imaging findings or they were excluded. χ(2) analysis was used to compare differences between subtypes, with multivariate logistic regression analysis used to assess for variable independence. RESULTS Identified were 289 (65.5%) luminal A, 45 (10.2%) luminal B, 26 (5.9%) HER2, and 81 (18.4%) basal subtypes. Among subtypes, significant differences were found in the frequency of multicentric and/or multifocal disease (luminal A, 27.3% [79 of 289]; luminal B, 53.3% [24 of 45]; HER2, 65.4% [17 of 26]; basal, 27.2% [22 of 81]; P < .001) and lymph node involvement (luminal A, 17.3% [50 of 289]; luminal B, 35.6% [26 of 45]; HER2, 34.6% [nine of 26]; basal 24.7% [20 of 81]; P = .014). Multivariate analysis showed that molecular subtype was independently predictive of multifocal and/or multicentric disease. CONCLUSION Preoperative breast MR imaging is significantly more likely to help detect multifocal and/or multicentric disease and lymph node involvement in luminal B and HER2 molecular subtype breast cancers. Molecular subtype may help to select patients for preoperative breast MR imaging.

Men (and Women) in Academic Radiology: How Can We Reduce the Gender Discrepancy?

OBJECTIVE There is a chronic gender imbalance in academic radiology departments, which could limit our fields ability to foster creative, productive, and innovative environments. We recently reviewed 51 major academic radiology faculty rosters and discovered that 34% of academic radiologists are women, but only 25% of vice chairs and section chiefs and 9% of department chairs are women. CONCLUSION Active intervention is needed to correct this imbalance, which should start with awareness of the issue, exposing medical students to radiology early in their training, and implementing better mentorship programs for female radiologists.

Incidental detection of nutcracker phenomenon on multidetector CT in an asymptomatic population: prevalence and associated findings.

Objective To determine the prevalence of nutcracker phenomenon (left renal vein compression by the superior mesenteric artery) and secondary anatomic findings using multidetector computed tomographic (CT) angiography in an asymptomatic population. Methods Ninety-nine consecutive CT angiograms for potential renal transplant donors (mean age, 39.0 years; 42 males) without variant renal vein anatomy were reviewed retrospectively. The diameters of the maximal left renal vein, left renal vein between the aorta and superior mesenteric artery, and draining gonadal and lumbar veins were measured. Sex, age, hematuria, proteinuria, and abdominal or flank pain were recorded. Results Twenty-three patients had 50% to 70% stenosis, and 4 patients had greater than 70% stenosis of the left renal vein. Dilated gonadal and lumbar veins were found in 16 and 28 patients, respectively. Four patients had hematuria. These findings were not significantly associated with left renal vein compression. Conclusions Nutcracker phenomenon and dilated veins originating from the left renal vein are common incidental CT findings and nonspecific for the diagnosis of nutcracker syndrome.

Interobserver Variability Between Breast Imagers Using the Fifth Edition of the BI-RADS MRI Lexicon.

OBJECTIVE The purpose of this study was to assess the interobserver variability of users of the MRI lexicon in the fifth edition of the BI-RADS atlas. MATERIALS AND METHODS Three breast imaging specialists reviewed 280 routine clinical breast MRI findings reported as BI-RADS category 3. Lesions reported as BI-RADS 3 were chosen because variability in the use of BI-RADS descriptors may influence which lesions are classified as probably benign. Each blinded reader reviewed every study and recorded breast features (background parenchymal enhancement) and lesion features (lesion morphology, mass shape, mass margin, mass internal enhancement, nonmass enhancement distribution, nonmass enhancement internal enhancement, enhancement kinetics) according to the fifth edition of the BI-RADS lexicon and provided a final BI-RADS assessment. Interobserver variability was calculated for each breast and lesion feature and for the final BI-RADS assessment. RESULTS Interobserver variability for background parenchymal enhancement was fair (ĸ = 0.28). There was moderate agreement on lesion morphology (ĸ = 0.53). For masses, there was substantial agreement on shape (ĸ = 0.72), margin (ĸ = 0.78), and internal enhancement (ĸ = 0.69). For nonmass enhancement, there was substantial agreement on distribution (ĸ = 0.69) and internal enhancement (ĸ = 0.62). There was slight agreement on lesion kinetics (ĸ = 0.19) and final BI-RADS assessment (ĸ = 0.11). CONCLUSION There is moderate to substantial agreement on most MRI BI-RADS lesion morphology descriptors, particularly mass and nonmass enhancement features, which are important predictors of malignancy. Considerable disagreement remains, however, among experienced readers whether to follow particular findings.

Breast MRI radiogenomics: Current status and research implications

Breast magnetic resonance imaging (MRI) radiogenomics is an emerging area of research that has the potential to directly influence clinical practice. Clinical MRI scanners today are capable of providing excellent temporal and spatial resolution, which allows extraction of numerous imaging features via human extraction approaches or complex computer vision algorithms. Meanwhile, advances in breast cancer genetics research has resulted in the identification of promising genes associated with cancer outcomes. In addition, validated genomic signatures have been developed that allow categorization of breast cancers into distinct molecular subtypes as well as predict the risk of cancer recurrence and response to therapy. Current radiogenomics research has been directed towards exploratory analysis of individual genes, understanding tumor biology, and developing imaging surrogates to genetic analysis with the long‐term goal of developing a meaningful tool for clinical care. The background of breast MRI radiogenomics research, image feature extraction techniques, approaches to radiogenomics research, and promising areas of investigation are reviewed. J. Magn. Reson. Imaging 2016;43:1269–1278.

Predictors of an Academic Career on Radiology Residency Applications

RATIONALE AND OBJECTIVES To evaluate radiology residency applications to determine if any variables are predictive of a future academic radiology career. MATERIALS AND METHODS Application materials from 336 radiology residency graduates between 1993 and 2010 from the Department of Radiology, Duke University and between 1990 and 2010 from the Department of Radiology, Stanford University were retrospectively reviewed. The institutional review boards approved this Health Insurance Portability and Accountability Act-compliant study with a waiver of informed consent. Biographical (gender, age at application, advanced degrees, prior career), undergraduate school (school, degree, research experience, publications), and medical school (school, research experience, manuscript publications, Alpha Omega Alpha membership, clerkship grades, United States Medical Licensing Examination Step 1 and 2 scores, personal statement and letter of recommendation reference to academics, couples match status) data were recorded. Listing in the Association of American Medical Colleges Faculty Online Directory and postgraduation publications were used to determine academic status. RESULTS There were 72 (21%) radiologists in an academic career and 264 (79%) in a nonacademic career. Variables associated with an academic career were elite undergraduate school (P = .003), undergraduate school publications (P = .018), additional advanced degrees (P = .027), elite medical school (P = .006), a research year in medical school (P < .001), and medical school publications (P < .001). A multivariate cross-validation analysis showed that these variables are jointly predictive of an academic career (P < .001). CONCLUSIONS Undergraduate and medical school rankings and publications, as well as a medical school research year and an additional advanced degree, are associated with an academic career. Radiology residency selection committees should consider these factors in the context of the residency application if they wish to recruit future academic radiologists.