Abbreviated Breast MRI for Supplemental Screening in Patients With Dense Breasts: Comparison of Baseline Versus Subsequent-Round Examinations.

BACKGROUND. Abbreviated breast MRI (AB-MRI) achieves a higher cancer detection rate (CDR) than digital breast tomosynthesis when applied for baseline (i.e., first-round) supplemental screening of individuals with dense breasts. Limited literature has evaluated subsequent (i.e., sequential) AB-MRI screening rounds. OBJECTIVE. This study aimed to compare outcomes between baseline and subsequent rounds of screening AB-MRI in individuals with dense breasts who otherwise had an average risk for breast cancer. METHODS. This retrospective study included patients with dense breasts who otherwise had an average risk for breast cancer and underwent AB-MRI for supplemental screening between December 20, 2016, and May 10, 2023. The clinical interpretations and results of recommended biopsies for AB-MRI examinations were extracted from the EMR. Baseline and subsequent-round AB-MRI examinations were compared. RESULTS. The final sample included 2585 AB-MRI examinations (2007 baseline and 578 subsequent-round examinations) performed for supplemental screening of 2007 women (mean age, 57.1 years old) with dense breasts. Of 2007 baseline examinations, 1658 (82.6%) were assessed as BI-RADS category 1 or 2, 171 (8.5%) as BI-RADS category 3, and 178 (8.9%) as BI-RADS category 4 or 5. Of 578 subsequent-round examinations, 533 (92.2%) were assessed as BI-RADS category 1 or 2, 20 (3.5%) as BI-RADS category 3, and 25 (4.3%) as BI-RADS category 4 or 5 (p < .001). The abnormal interpretation rate (AIR) was 17.4% (349/2007) for baseline examinations versus 7.8% (45/578) for subsequent-round examinations (p < .001). For baseline examinations, PPV2 was 21.3% (38/178), PPV3 was 26.6% (38/143), and the CDR was 18.9 cancers per 1000 examinations (38/2007). For subsequent-round examinations, PPV2 was 28.0% (7/25) (p = .45), PPV3 was 29.2% (7/24) (p = .81), and the CDR was 12.1 cancers per 1000 examinations (7/578) (p = .37). All 45 cancers diagnosed by baseline or subsequent-round AB-MRI were stage 0 or 1. Seven cancers diagnosed by subsequent-round AB-MRI had a mean interval of 872 ± 373 (SD) days since prior AB-MRI and node-negative status at surgical axillary evaluation; six had an invasive component, all measuring 1.2 cm or less. CONCLUSION. Subsequent rounds of AB-MRI screening of individuals with dense breasts had lower AIR than baseline examinations while maintaining a high CDR. All cancers detected by subsequent-round examinations were early-stage node-negative cancers. CLINICAL IMPACT. The findings support sequential AB-MRI for supplemental screening in individuals with dense breasts. Further investigations are warranted to optimize the screening interval.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Breast MRI: False-Negative Results and Missed Opportunities.

Breast MRI is the most sensitive modality for the detection of breast cancer. However, false-negative cases may occur, in which the cancer is not visualized at MRI and is instead diagnosed with another imaging modality. The authors describe the causes of false-negative breast MRI results, which can be categorized broadly as secondary to perceptual errors or cognitive errors, or nonvisualization secondary to nonenhancement of the tumor. Tips and strategies to avoid these errors are discussed. Perceptual errors occur when an abnormality is not prospectively identified, yet the examination is technically adequate. Careful development of thorough search patterns is critical to avoid these errors. Cognitive errors occur when an abnormality is identified but misinterpreted or mischaracterized as benign. The radiologist may avoid these errors by utilizing all available prior examinations for comparison, viewing images in all planes to better assess the margins and shapes of abnormalities, and appropriately integrating all available information from the contrast-enhanced, T2-weighted, and T1-weighted images as well as the clinical history. Despite this, false-negative cases are inevitable, as certain subtypes of breast cancer, including ductal carcinoma in situ, invasive lobular carcinoma, and certain well-differentiated invasive cancers, may demonstrate little to no enhancement at MRI, owing to differences in angiogenesis and neovascularity. MRI is a valuable diagnostic tool in breast imaging. However, MRI should continue to be used as a complementary modality, with mammography and US, in the detection of breast cancer. ©RSNA, 2021.

Five Consecutive Years of Screening with Digital Breast Tomosynthesis: Outcomes by Screening Year and Round.

Background Limited data exist beyond prevalence rounds of digital breast tomosynthesis (DBT) screening. Purpose To compare DBT outcomes over multiple years and rounds to outcomes of digital mammography (DM) screening. Materials and Methods Retrospective analysis included 1 year of DM and 5 years of DBT screening (September 2011 to September 2016); 67 350 examinations were performed in 29 310 women. Recall rate (RR) percentage, cancer detection rate (CDR) per 1000 women screened, false-negative rate per 1000 women screened, positive predictive value of recall (PPV1) percentage, positive predictive value of biopsies performed percentage, sensitivity, and specificity were calculated. Cancers diagnosed within 1 year of screening were captured by means of linkage to state cancer registry, and biologic characteristics were grouped by prognostic factors. Performance trends across DBT rounds were compared with those from DM rounds by using logistic regression to account for examinations in the same woman. Analyses were adjusted for age, race, breast density, baseline examination, and reader. Results There were 56 839 DBT and 10 511 DM examinations. The mean patient age (± standard deviation) was 56 years ±11 for the entire cohort, 55 years ±11 for the DBT group, and 57 years ±11 for the DM group. RRs were significantly lower for the DBT group (8.0%, 4522 of 56 839; 95% confidence interval [CI]: 7.7, 8.2) than for the DM group (10.4%, 1094 of 10 511; 95% CI: 9.8, 11.0) (P < .001). CDRs were higher with DBT (6.0 per 1000 women screened; 95% CI: 5.4, 6.7 per 1000 women screened; 340 of 56 839) than with DM (5.1 per 1000 women screened; 95% CI: 3.9, 6.6 per 1000 women screened; 54 of 10 511) (P = .25), but this difference was not statistically significant. Both RR and CDR remained improved compared with DM for 5 years of DBT at the population level. False-negative rates were slightly lower for DBT (0.6 per 1000 women screened; 95% CI: 0.4, 0.8 per 1000 women screened; 33 of 56 839) than DM (0.9 per 1000 women screened; 0.4, 1.6 per 1000 women screened; nine of 10 511) overall (P = .30), but the difference was not statistically significant. In adjusted analyses, RR, biopsy recommendation rates, and PPV1 were improved for DBT versus DM (P ≤ .001). Compared with DM, a higher proportion of DBT-detected cancers were invasive (70% [238 of 340] vs 68.5% [37 of 54]) and had poor prognoses characteristics (32.6% [76 of 233] vs 25.0% [nine of 36]). Conclusion Favorable outcomes with digital breast tomosynthesis screening were sustained over multiple years and rounds. Digital breast tomosynthesis screening was associated with detection of a higher proportion of poor-prognosis cancers than was digital mammography. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Moy and Heller in this issue.

Effect of contrast dose on diagnostic performance in DCE-MR breast imaging.

OBJECTIVE: To assess the diagnostic performance of breast magnetic resonance (MR) imaging as a function of gadolinium contrast dose using a retrospective reader study. MATERIAL AND METHODS: IRB approval was obtained prior to the start of this study and was HIPAA compliant. One-hundred and fifty MR breast examinations were included that were acquired between January 2001 and December 2006. Seventy-five patients received contrast doses (gadopentetate dimeglumine) by weight of 0.10 mmol/kg and 75 patients were imaged using fixed volumes of 20 ml. The images were assessed by two radiologists with performance calculated for each reader as well as a combined assessment. Dose response was measured by comparing performance between cases binned by dose: <=0.10; >0.10; and >0.13 mmol/kg. Statistical significance was calculated using a one-sided Z-test for differences in proportions with interobserver agreement calculated using Cohen's kappa statistics. RESULTS: In the combined reader assessment with equivocal lesions classified as negative, sensitivity rose from 66% (19/29) to 92% (24/26, P < 0.01) and 95% (18/19, P < 0.01) with the specificity also increasing from 65% (32/49) to 87% (40/46, P < 0.01) and 86% (32/37, P = 0.01) corresponding to doses <=0.10, >0.10, >0.13 mmol/kg. With equivocal lesions classified as positive, sensitivity rose from 79% (23/29) to 92% (24/26, P < 0.10) and 95% (18/19, P < 0.10) Specificity also increased from 53% (26/49) to 72% (33/46, P < 0.05) and 70% (26/37, P = 0.05) with increasing dose. Interobserver agreement also improved at the higher doses.

Digital Breast Tomosynthesis: Concepts and Clinical Practice.

Digital breast tomosynthesis (DBT) is emerging as the standard of care for breast imaging based on improvements in both screening and diagnostic imaging outcomes. The additional information obtained from the tomosynthesis acquisition decreases the confounding effect of overlapping tissue, allowing for improved lesion detection, characterization, and localization. In addition, the quasi three-dimensional information obtained from the reconstructed DBT data set allows a more efficient imaging work-up than imaging with two-dimensional full-field digital mammography alone. Herein, the authors review the benefits of DBT imaging in screening and diagnostic breast imaging.

Breast Cancer Conspicuity on Simultaneously Acquired Digital Mammographic Images versus Digital Breast Tomosynthesis Images.

Background Digital breast tomosynthesis (DBT) has been shown to improve screening outcomes compared with digital mammography (DM) alone. However, little is known about differences in breast cancer conspicuity between DM and DBT or by mammographic view. Purpose To compare conspicuity of breast cancers at DM versus DBT and by mammographic view, craniocaudal (CC) versus mediolateral oblique (MLO). Materials and Methods Lesion conspicuity was graded by three readers by using a 0-5 numerical scale on both DM and DBT images from combined DM and DBT studies for 197 consecutive screening-detected cancers in women (mean age, 60.4 years ± 11.1 [standard deviation]) from October 1, 2011, through December 31, 2014. Intermodality (ie, DM vs DBT) and intramodality (ie, CC vs MLO) analyses were performed. For intramodality analyses, conspicuity was analyzed by view, CC versus MLO, within the same modality. Conspicuity grades were dichotomized into low (scores 0-3) and high (scores 4 and 5) conspicuity. This binary result was assessed by using a generalized linear mixed-effects model with logit link function, random-effect intercept for reader, and compound symmetry covariance structure for lesion. Results Cancers were more likely to be high conspicuity at DBT than at DM (odds ratio [OR], 2.4; 95% confidence interval [CI]: 1.9, 3.0; P < .01). At both DM and DBT, cancers were more likely to be high conspicuity at the CC than the MLO view (DM vs DBT OR, 1.6 [95% CI: 1.3, 1.9] vs 1.7 [95% CI: 1.3, 2.1], respectively; P < .01 for both). Cancers seen at one view only were more often detected at CC than MLO for both DM and DBT (DM vs DBT OR, 1.6 [95% CI: 1.2, 2.0] vs 3.6 [95% CI: 1.9, 7.0], respectively; P < .01.). Conclusion Cancers were more conspicuous at digital breast tomosynthesis than at digital mammography. Cancers may only be detected at one of two views, and they are more likely to be seen at the craniocaudal view. © RSNA, 2019.

Characterizing and eliminating errors in enhancement and subtraction artifacts in dynamic contrast-enhanced breast MRI: Chemical shift artifact of the third kind.

PURPOSE: To characterize errors in enhancement in breast dynamic contrast-enhanced (DCE) MRI studies as a function of echo time and determine the source of dark band artifacts in clinical subtraction images. METHODS: Computer simulations, oil and water substitute (methylene chloride), as well as an American College of Radiology quality control phantom were tested. Routine clinical DCE breast MRI study was bracketed with (accelerated) in-phase DCE acquisitions in five patients. RESULTS: Simulation results demonstrated up to -160% suppression of the expected enhancement caused by differential enhancement of fat and water. Two-dimensional gradient-recalled echo and fat-suppressed 3D GRE phantom imaging confirmed the simulation results and showed that fat suppression does not eliminate the artifact. In vivo in-phase DCE images showed increased enhancement consistent with predictions and also confirmed increased spatial blurring on in-phase 3D gradient-recalled echo images. Combined multi-dimensional partial Fourier and parallel imaging provided a time-equivalent in-phase DCE MRI acquisition. CONCLUSION: Errors in expected enhancement occur in DCE breast MRI subtraction images because of differential enhancement of fat and water and incomplete fat signal suppression. These errors can lead to artificial suppression of enhancement as well as dark band artifacts on subtraction images. These artifacts can be eliminated with a time-equivalent in-phase fat-suppressed 3D gradient-recalled echo sequence. Understanding chemical shift artifact of the third kind, a unique artifact of artificial enhancement suppression in the presence of intravoxel fat and water signal, will aid DCE breast MRI image interpretation. In-phase acquisitions (combined with simultaneous minimum echo time or opposed-phase echoes) may facilitate qualitative, quantitative and longitudinal analysis of contrast enhancement. Magn Reson Med 79:2277-2289, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The impact of preoperative magnetic resonance imaging and lumpectomy cavity shavings on re-excision rate in pure ductal carcinoma in situ-A single institution's experience.

BACKGROUND AND OBJECTIVES: The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re-excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS. METHODS: This is a single-institution retrospective study of 295 women undergoing breast conservation surgery for pure DCIS (2010-2013). CSM were the systematic resection of 4-6 margins during lumpectomy whereas selective shave margins (SSM) were the selective resection of 1-3 margins. Patient demographics and clinical characteristics were abstracted. RR was analyzed according to the use of pMRI, SSM, or CSM with respect to three high-volume breast surgeons at our institution. RESULTS: RR was not associated with the use of pMRI (P = 0.87). Any shave margins (P = 0.05), DCIS size (P < 0.001), and DCIS grade (P = 0.14) associated with a lower RR. Of our high-volume surgeons, RR was lower for Surgeon A (P = 0.02). Multivariate analyses showed larger DCIS (OR 1.35, P = 0.005) and practices specific to surgeons B (OR 3.23, P = 0.04) and C (OR 3.57, P = 0.04) increased re-excision odds. CONCLUSIONS: SSM/CSM and pMRI use varied among surgeons. Our results suggested the routine use of CSM, not pMRI, could lower re-excision rate, which highlighted a quality improvement opportunity at our institution.

Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells.

The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation.

BI-RADS Category 3 Comparison: Probably Benign Category after Recall from Screening before and after Implementation of Digital Breast Tomosynthesis.

Purpose To evaluate Breast Imaging Reporting and Data System (BI-RADS) category 3 assessment at diagnostic examination after recall from screening in a large urban population after implementation of digital breast tomosynthesis (DBT) by focusing both on overall use and use stratified by recalled finding type and outcome at 2 years. Materials and Methods This was an intuitional review board-approved and HIPAA-compliant retrospective review of 10 728 digital mammography (DM) examinations from September 1, 2010, to August 30, 2011, and 15 571 screening DBT examinations from October 1, 2011, to February 28, 2013. The recall populations for DM and DBT were 1112 of 10 728 (10.4% of women screened) and 1366 of 15 571 (8.8% of women screened), respectively. Recall examinations were classified according to finding type: calcifications, asymmetry or focal asymmetry, mass, and architectural distortion. Differences between groups were compared by using the χ2 test. Results Although there was no significant change in the utilization rate of BI-RADS category 3 in those patients screened with DM compared with DBT (168 of 10 728, 1.6% for DM vs 206 of 15 571, 1.3% for DBT; P = .102), there was a mean overall reduction of 2.4 women per 1000 (95% confidence interval [CI]: -0.5, 5.4) recommended for short-term follow-up. Lesion types given a BI-RADS category 3 assessment after diagnostic work-up did not change. The distribution of recalled finding types significantly changed with DBT, with increased recall examinations for architectural distortion and mass (P < .001) and decreased recall examinations for asymmetries (P ≤ .001). There was no change in recall examinations for calcifications (P = .977). Conclusion Screening with DBT did not significantly change the utilization rate of BI-RADS category 3 classification; however, the overall number of patients recommended for short-interval follow-up decreased by a mean of 2.4 women per 1000 (95% CI: -0.5, 5.4). © RSNA, 2017 Online supplemental material is available for this article.

Agreement between Breast Percentage Density Estimations from Standard-Dose versus Synthetic Digital Mammograms: Results from a Large Screening Cohort Using Automated Measures.

Purpose To evaluate agreement between automated estimates of breast density made from standard-dose versus synthetic digital mammograms in a large cohort of women undergoing screening. Materials and Methods This study received institutional review board approval with waiver of consent. A total of 3668 negative (Breast Imaging Reporting and Data System category 1 or 2) digital breast tomosynthesis (DBT) screening examinations consecutively performed over a 4-month period at one institution for which both standard-dose and synthetic mammograms were available for analysis were retrospectively analyzed. All mammograms were acquired with a Selenia Dimensions system (Hologic, Bedford, Mass), and synthetic mammograms were generated by using the U.S. Food and Drug Administration-approved "C-View" software module. The "For Presentation" standard-dose mammograms and synthetic images were analyzed by using a fully automated algorithm. Agreement between density estimates was assessed by using Pearson correlation, linear regression, and Bland-Altman analysis. Differences were evaluated by using the paired Student t test. Results Breast percentage density (PD) estimates from synthetic and standard-dose mammograms were highly correlated (r = 0.92, P < .001), and the 95% Bland-Altman limits of agreement between PD estimates were -6.4% to 9.9%. Synthetic mammograms had PD estimates by an average of 1.7% higher than standard-dose mammograms (P < .001), with a larger disagreement by 1.56% in women with highly dense breast tissue (P < .0001). Conclusion Fully automated estimates of breast density made from synthetic mammograms are generally comparable to those made from standard-dose mammograms. This may be important, as standard two-dimensional mammographic images are increasingly being replaced by synthetic mammograms in DBT screening in an attempt to reduce radiation dose. © RSNA, 2017 Online supplemental material is available for this article.

Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer.

BACKGROUND: In human epidermal growth factor 2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2+BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2+BC. METHODS: A retrospective review of HER2+BC patients at the authors' institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed. RESULTS: For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53-418), and

Imaging With Synthesized 2D Mammography: Differences, Advantages, and Pitfalls Compared With Digital Mammography.

OBJECTIVE: Synthesized 2D (s2D) mammography is rapidly replacing digital mammography in breast imaging with digital breast tomosynthesis (DBT) to reduce radiation dose and maintain screening outcomes. We illustrate variations in the appearance of s2D and digital mammograms to aid in implementation of this technology. CONCLUSION: Despite subjective differences in the appearance of s2D and digital mammograms, early outcomes of screening using s2D mammography and DBT are not inferior to those achieved with digital mammography and DBT. Understanding these variations may aid in implementing this technique and improving patient outcomes.

Molecular Probes for Imaging the Sigma-2 Receptor: In Vitro and In Vivo Imaging Studies.

The sigma-2 (σ2) receptor has been validated as a biomarker of the proliferative status of solid tumors. Therefore, radiotracers having a high affinity and high selectivity for σ2 receptors have the potential to assess the proliferative status of human tumors using noninvasive imaging techniques such as Positron Emission Tomography (PET). Since the σ2 receptor has not been cloned, the current knowledge of this receptor has relied on receptor binding studies with the radiolabeled probes and investigation of the effects of the σ2 receptor ligands on tumor cells. The development of the σ2 selective fluorescent probes has proven to be useful for studying subcellular localization and biological functions of the σ2 receptor, for revealing pharmacological properties of the σ2 receptor ligands, and for imaging cell proliferation. Preliminary clinical imaging studies with [18F]ISO-1, a σ2 receptor probe, have shown promising results in cancer patients. However, the full utility of imaging the σ2 receptor status of solid tumors in the diagnosis and prediction of cancer therapeutic response will rely on elucidation of the functional role of this protein in normal and tumor cell biology.

Fully Automated Quantitative Estimation of Volumetric Breast Density from Digital Breast Tomosynthesis Images: Preliminary Results and Comparison with Digital Mammography and MR Imaging.

PURPOSE: To assess a fully automated method for volumetric breast density (VBD) estimation in digital breast tomosynthesis (DBT) and to compare the findings with those of full-field digital mammography (FFDM) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Bilateral DBT images, FFDM images, and sagittal breast MR images were retrospectively collected from 68 women who underwent breast cancer screening from October 2011 to September 2012 with institutional review board-approved, HIPAA-compliant protocols. A fully automated computer algorithm was developed for quantitative estimation of VBD from DBT images. FFDM images were processed with U.S. Food and Drug Administration-cleared software, and the MR images were processed with a previously validated automated algorithm to obtain corresponding VBD estimates. Pearson correlation and analysis of variance with Tukey-Kramer post hoc correction were used to compare the multimodality VBD estimates. RESULTS: Estimates of VBD from DBT were significantly correlated with FFDM-based and MR imaging-based estimates with r = 0.83 (95% confidence interval [CI]: 0.74, 0.90) and r = 0.88 (95% CI: 0.82, 0.93), respectively (P < .001). The corresponding correlation between FFDM and MR imaging was r = 0.84 (95% CI: 0.76, 0.90). However, statistically significant differences after post hoc correction (α = 0.05) were found among VBD estimates from FFDM (mean ± standard deviation, 11.1% ± 7.0) relative to MR imaging (16.6% ± 11.2) and DBT (19.8% ± 16.2). Differences between VDB estimates from DBT and MR imaging were not significant (P = .26). CONCLUSION: Fully automated VBD estimates from DBT, FFDM, and MR imaging are strongly correlated but show statistically significant differences. Therefore, absolute differences in VBD between FFDM, DBT, and MR imaging should be considered in breast cancer risk assessment.

The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006.

Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI-RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88-0.95; weighted κ = 0.83-0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76-0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. (©) RSNA, 2016 Online supplemental material is available for this article.

Implementation of Synthesized Two-dimensional Mammography in a Population-based Digital Breast Tomosynthesis Screening Program.

Purpose To evaluate the early implementation of synthesized two-dimensional (s2D) mammography in a population screened entirely with s2D and digital breast tomosynthesis (DBT) (referred to as s2D/DBT) and compare recall rates and cancer detection rates to historic outcomes of digital mammography combined with DBT (referred to as digital mammography/DBT) screening. Materials and Methods This was an institutional review board-approved and HIPAA-compliant retrospective interpretation of prospectively acquired data with waiver of informed consent. Compared were recall rates, biopsy rates, cancer detection rates, and radiation dose for 15 571 women screened with digital mammography/DBT from October 1, 2011, to February 28, 2013, and 5366 women screened with s2D/DBT from January 7, 2015, to June 30, 2015. Two-sample z tests of equal proportions were used to determine statistical significance. Results Recall rate for s2D/DBT versus digital mammography/DBT was 7.1% versus 8.8%, respectively (P < .001). Biopsy rate for s2D/DBT versus digital mammography/DBT decreased (1.3% vs 2.0%, respectively; P = .001). There was no significant difference in cancer detection rate for s2D/DBT versus digital mammography/DBT (5.03 of 1000 vs 5.45 of 1000, respectively; P = .72). The average glandular dose was 39% lower in s2D/DBT versus digital mammography/DBT (4.88 mGy vs 7.97 mGy, respectively; P < .001). Conclusion Screening with s2D/DBT in a large urban practice resulted in similar outcomes compared with digital mammography/DBT imaging. Screening with s2D/DBT allowed for the benefits of DBT with a decrease in radiation dose compared with digital mammography/DBT. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on August 11, 2016.