Sujata V. Ghate

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.

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.

MRI-guided vacuum-assisted breast biopsy with a handheld portable biopsy system.

OBJECTIVE The purpose of this study was to evaluate a compact portable 10-gauge handheld battery-operated vacuum-assisted biopsy system for MRI-guided breast biopsy. CONCLUSION The compact portable battery-operated biopsy system can be used successfully for MRI-guided core breast biopsy and is an alternative to current systems.

Is Surgical Excision of Core Biopsy Proven Benign Papillomas of the Breast Necessary

RATIONALE AND OBJECTIVES The aim of this study was to determine if core biopsy-proven benign papillomas of the breast need to be surgically excised. MATERIALS AND METHODS Mammographic and pathologic database review from January 1994 to January 2004 revealed 178 papillary lesions diagnosed by core biopsy in 176 women (mean age, 59 years). All lesions had >or=24 months of imaging follow-up (n = 75) or surgical correlation (n = 103). Details regarding core biopsy technique, lesion appearance, pathologic results, imaging-histopathologic concordance, and follow-up imaging were recorded. Core and surgical pathologic results were correlated. RESULTS Of the 178 papillary lesions diagnosed at core needle biopsy, 120 (67%) were initially diagnosed as benign without atypia. The core biopsy diagnoses of benignity were confirmed for all 120 lesions by either surgical excision (n = 45) or stability after >or=2 years of imaging follow-up (n = 75). Of the remaining 58 papillary lesions, 50 were found to be atypical at core needle biopsy; 15 of those 50 (29%) were upgraded to malignancies at surgical excision. Eight of the 178 lesions (5%) were initially diagnosed as malignant papillary lesions at core needle biopsy. Seven of these eight (88%) were confirmed malignant at excision. None of the surgically proven cancers was diagnosed as benign at core biopsy. CONCLUSIONS Close imaging follow-up rather than excision of core biopsy-proven benign papillomas was adequate given careful imaging-histopathologic correlation and excision of all atypical and discordant lesions. Individual centers should evaluate their own data and tailor their practices accordingly.

Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

PURPOSE Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. METHODS The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. RESULTS The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images were in general agreement with real human images. The Singlet approach offered more realistic contrast as compared to the Doublet approach, but at the expense of air bubbles and air pockets that formed during the filling process. CONCLUSIONS The presented physical breast phantoms and their matching virtual breast phantoms offer realistic breast anatomy, patient variability, and ease of use, making them a potential candidate for performing both system quality control testing and virtual clinical trials.

Sonohysterography: Do 3D Reconstructed Images Provide Additional Value?

OBJECTIVE The purpose of this study was to retrospectively determine the value of adding 3D multiplanar sonography to 2D sonohysterography. MATERIALS AND METHODS Between September 2003 and April 2005, 80 women (mean age, 43.5 years; range, 26-78 years) underwent sonohysterography with both conventional 2D sonohysterography and 3D multiplanar imaging (volume of data acquired and reconstructed in the transverse, sagittal, and coronal planes). Three blinded readers interpreted the 2D scans alone and then the 2D and 3D images together. Visualization of endometrial abnormality (polyps, fibroids, or septations) and definition of fundal contour were scored by each reader on a three-point scale (1, visualized; 2, unsure; 3, not visualized). Wilcoxons signed rank test was used to assess mean differences between findings. Reader agreement was determined with the kappa statistic. Pathologic correlation was performed when the findings were available. RESULTS Average (mean +/- SD) reader scores for identification of endometrial abnormality were not significantly different: 1.70 +/- 0.91 for 2D alone versus 1.69 +/- 0.92 for 2D and 3D combined (p = 0.38). There also was no significant difference when polyps (2.14 +/- 0.90 vs 2.12 +/- 0.93), fibroids (2.57 +/- 0.79 vs 2.53 +/- 0.82), and septations (2.88 +/- 0.39 vs 2.87 +/- 0.42) were evaluated separately. Average scores for definition of fundal contour were significantly (p < 0.0001) different (2.93 +/- 0.34 for 2D alone versus 1.45 +/- 0.80 for 2D and 3D combined). Agreement between readers was found with average kappa values of 0.72 for 2D alone and 0.78 for 2D and 3D. For the 42 subjects for whom pathologic findings were available, readers identified 92% of the abnormalities. CONCLUSION Three-dimensional reformations improve visualization of the uterine fundus and aid in identification or exclusion of a fundal contour abnormality but do not add value in the detection of endometrial abnormalities.

Breast self-examination: defining a cohort still in need

BACKGROUND The value of breast self-examination (BSE) to detect early breast cancer is controversial. METHODS Within an institutional review board-approved prospective study, 147 high-risk women were enrolled from 2004 to 2007. Yearly clinical examination, BSE teaching, and mammography were performed simultaneously followed by interval breast magnetic resonance imaging (MRI). Women underwent additional BSE teaching at 6 months. Women reporting a mass on BSE underwent clinical evaluation. RESULTS Fourteen breast cancers were detected in 12 women. BSE detected 6/14 breast cancers versus 6/14 detected by MRI and 2/14 by mammography. Of 24 masses detected by BSE, 6/24 were malignant. The sensitivity, specificity, and predictive value of BSE to detect breast cancer were 58.3%, 87.4%, and 29.2%, respectively. The sensitivity, specificity, and predictive value of a Breast Image Reporting and Data System (BI-RADS) score of >or=4 on MRI were 66.7%, 88.9%, and 34.8%, respectively. CONCLUSIONS BSE detects new breast cancers in high-risk women undergoing screening mammogram, CBE, and yearly breast MRI.

Development and Application of a Suite of 4-D Virtual Breast Phantoms for Optimization and Evaluation of Breast Imaging Systems

Mammography is currently the most widely utilized tool for detection and diagnosis of breast cancer. However, in women with dense breast tissue, tissue overlap may obscure lesions. Digital breast tomosynthesis can reduce tissue overlap. Furthermore, imaging with contrast enhancement can provide additional functional information about lesions, such as morphology and kinetics, which in turn may improve lesion identification and characterization. The performance of these imaging techniques is strongly dependent on the structural composition of the breast, which varies significantly among patients. Therefore, imaging system and imaging technique optimization should take patient variability into consideration. Furthermore, optimization of imaging techniques that employ contrast agents should include the temporally varying breast composition with respect to the contrast agent uptake kinetics. To these ends, we have developed a suite of 4-D virtual breast phantoms, which are incorporated with the kinetics of contrast agent propagation in different tissues and can realistically model normal breast parenchyma as well as benign and malignant lesions. This development presents a new approach in performing simulation studies using truly anthropomorphic models. To demonstrate the utility of the proposed 4-D phantoms, we present a simplified example study to compare the performance of 14 imaging paradigms qualitatively and quantitatively.

Comparative performance of multiview stereoscopic and mammographic display modalities for breast lesion detection

PURPOSE Mammography is known to be one of the most difficult radiographic exams to interpret. Mammography has important limitations, including the superposition of normal tissue that can obscure a mass, chance alignment of normal tissue to mimic a true lesion and the inability to derive volumetric information. It has been shown that stereomammography can overcome these deficiencies by showing that layers of normal tissue lay at different depths. If standard stereomammography (i.e., a single stereoscopic pair consisting of two projection images) can significantly improve lesion detection, how will multiview stereoscopy (MVS), where many projection images are used, compare to mammography? The aim of this study was to assess the relative performance of MVS compared to mammography for breast mass detection. METHODS The MVS image sets consisted of the 25 raw projection images acquired over an arc of approximately 45 degrees using a Siemens prototype breast tomosynthesis system. The mammograms were acquired using a commercial Siemens FFDM system. The raw data were taken from both of these systems for 27 cases and realistic simulated mass lesions were added to duplicates of the 27 images at the same local contrast. The images with lesions (27 mammography and 27 MVS) and the images without lesions (27 mammography and 27 MVS) were then postprocessed to provide comparable and representative image appearance across the two modalities. All 108 image sets were shown to five full-time breast imaging radiologists in random order on a state-of-the-art stereoscopic display. The observers were asked to give a confidence rating for each image (0 for lesion definitely not present, 100 for lesion definitely present). The ratings were then compiled and processed using ROC and variance analysis. RESULTS The mean AUC for the five observers was 0.614 +/- 0.055 for mammography and 0.778 +/- 0.052 for multiview stereoscopy. The difference of 0.164 +/- 0.065 was statistically significant with a p-value of 0.0148. CONCLUSIONS The differences in the AUCs and the p-value suggest that multiview stereoscopy has a statistically significant advantage over mammography in the detection of simulated breast masses. This highlights the dominance of anatomical noise compared to quantum noise for breast mass detection. It also shows that significant lesion detection can be achieved with MVS without any of the artifacts associated with tomosynthesis.

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.