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Many factors are involved in the successful development of early career breast imaging radiologists into independent investigators conducting impactful research. Key basic prerequisites for success include a motivated and resilient radiologist, institutional and departmental commitment to supporting early career physician-scientists, strong mentorship, and a flexible strategy for extramural funding that accounts for individualized professional goals. In this review, we describe these factors in greater detail, providing a practical overview for residents, fellows, and junior faculty who are interested in an academic career as a breast imaging radiologist engaged in original scientific research. We also describe the essential pieces of grant applications and summarize the professional milestones for early career physician-scientists as they look toward promotion to associate professor and sustained extramural funding.

Breast MRI is the most sensitive imaging modality for the assessment of newly diagnosed breast cancer extent and can detect additional mammographically and clinically occult breast cancers in the ipsilateral and contralateral breasts. Nonetheless, appropriate use of breast MRI in the setting of newly diagnosed breast cancer remains debated. Though highly sensitive, MRI is less specific and may result in false positives and overestimation of disease when MRI findings are not biopsied prior to surgical excision. Furthermore, improved anatomic depiction of breast cancer on MRI has not consistently translated to improved clinical outcomes, such as lower rates of re-excision or breast cancer recurrence, though there is a paucity of well-designed studies examining these issues. In addition, current treatment paradigms have been developed in the absence of this more accurate depiction of disease span, which likely has limited the value of MRI. These issues have led to inconsistent and variable utilization of preoperative MRI across practice settings and providers. In this review, we discuss the history of breast MRI and its current use and recommendations with a focus on the preoperative setting. We review the evidence surrounding the use of preoperative MRI in the evaluation of breast malignancies and discuss the data on breast MRI in the setting of specific patient factors often used to determine breast MRI eligibility, such as age, index tumor phenotype, and breast density. Finally, we review the impact of breast MRI on surgical outcomes (re-excision and mastectomy rates) and long-term breast recurrence and survival outcomes.

Introduction: In triple-negative breast cancer (TNBC), both response to neoadjuvant chemotherapy (NAC) and the degree of pre-treatment (pre-tx) tumor immune infiltration as defined by tumor-infiltrating lymphocytes (TILs) are prognostic. Improving NAC response prediction in early TNBC would provide the opportunity to consider adjustments to the NAC regimen prior to initiating therapy. Breast magnetic resonance imaging (MRI) enables noninvasive whole-tumor measurement of microenvironment features. We investigated the value of pre-tx MRI metrics in addition to TILs for the prediction of NAC response in early TNBC patients. Methods: Women with Stage I-III TNBC who underwent pre-tx clinical breast MRI and NAC at our institution (2005-2019) were retrospectively identified. Response to NAC was noted, with pathologic complete response (pCR) defined as no residual invasive cancer present within the breast. When tissue was available, diagnostic biopsy was used to quantify pre-tx TILs as deciles from 10-100% by a breast pathologist. Patients underwent pre-tx breast MRI on either a 1.5T or 3T scanner including diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) MRI. From DCE-MRI, tumor longest diameter (LD) and T stage (1-4), as well as contrast kinetics including percent enhancement (PE) at 2 minutes post-contrast and signal enhancement ratio (SER) were determined. Tumor peak PE and peak SER (representing the highest mean PE and SER, respectively, for 3×3 voxel subregions) and functional tumor volume (FTV, tumor volume exhibiting PE ≥ 50%) were calculated. Mean apparent diffusion coefficient (ADC) was calculated from DW-MRI. TIL levels and imaging features were compared between pCR and non-pCR groups by Wilcoxon rank sum test and performance for prediction of pCR was evaluated using areas under the curve (AUC) measures from receiver operating characteristic curve analysis. Results: 115 TNBC patients (median age: 49, range 26-79 years) were evaluated, of which 45 (39%) achieved pCR. The majority received an anthracycline-containing regimen. Pre-tx TILs (evaluated in N=60 with available biopsy specimens) ranged from 10% to 80% (median, 10%) and were significantly higher in pCR vs. non-pCR patients (p = 0.02, AUC = 0.63). Pre-tx lesion size on imaging was predictive of response (Table 1), with pCR patients having significantly lower LD (p < 0.01, AUC = 0.68) and FTV (p = 0.01, AUC = 0.67). Peak PE was also associated with response, significantly lower in pCR patients (p = 0.04, AUC = 0.62), while SER and ADC were not (p > 0.05). Stratifying by T stage, both peak PE (p = 0.03) and FTV (p = 0.05) were predictive of response in T1/T2 patients, while no imaging metrics reached significance in T3/T4 patients. Discussion: In a large cohort of TNBC patients undergoing NAC, measures of tumor size and immune infiltration were strongly predictive of NAC response. Preliminary results suggest that baseline peak PE and FTV are associated with NAC response, particularly in earlier stage TNBC patients. These findings support the utility of imaging and TILs assessments to predict response in TNBC and potentially guide NAC regimens for improved outcomes. Future work will extend these analyses to assess the value of changes in imaging metrics over the course of NAC to predict response. Acknowledgments: NIH P30CA015704, R01CA248192, and Roger E. Moe Fellowship, ASCO/CCF Hayden Family Foundation Young Investigator Award in Breast Cancer Summary of imaging characteristics across TNBC cohort. Values indicate mean (standard deviation).Whole cohort. N=115T1/T2. N=80T3/T4. N=35pCR. N=45non-pCR. N=70pAUCpCR. N=39non-pCR. N=41pAUCpCR. N=6non-pCR. N=29pAUCLongest dimension (mm)34 (15)50 (27) Citation Format: Anum S Kazerouni, Laura C. Kennedy, Michael Hirano, Bonny Chau, Debosmita Biswas, Shaveta Vinayak, Matthew J. Nyflot, Habib Rahbar, Suzanne Dintzis, Savannah C. Partridge. Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-08.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive cancer, and its detection, diagnosis, and management are controversial. DCIS incidence grew with the expansion of screening mammography programs in the 1980s and 1990s, and DCIS is viewed as a major driver of overdiagnosis and overtreatment. For pathologists, the diagnosis and classification of DCIS is challenging due to undersampling and interobserver variability. Understanding the progression from normal breast tissue to DCIS and, ultimately, to invasive cancer is limited by a paucity of natural history data with multiple proposed evolutionary models of DCIS initiation and progression. Although radiologists are familiar with the classic presentation of DCIS as asymptomatic calcifications at mammography, the expanded pool of modalities, advanced imaging techniques, and image analytics have identified multiple potential biomarkers of histopathologic characteristics and prognosis. Finally, there is growing interest in the nonsurgical management of DCIS, including active surveillance, to reduce overtreatment and provide patients with more personalized management options. However, current biomarkers are not adept at enabling identification of occult invasive disease at biopsy or accurately predicting the risk of progression to invasive disease. Several active surveillance trials are ongoing and are expected to better identify women with low-risk DCIS who may avoid surgery. © RSNA, 2021

Screening mammography reduces breast cancer mortality; however, when used to examine women with dense breasts, its performance and resulting benefits are reduced. Increased breast density is an independent risk factor for breast cancer. Digital breast tomosynthesis (DBT), ultrasound (US), molecular breast imaging (MBI), MRI, and contrast-enhanced mammography (CEM) each have shown improved cancer detection in dense breasts when compared with 2D digital mammography (DM). DBT is the preferred mammographic technique for producing a simultaneous reduction in recalls (i.e., additional imaging). US further increases cancer detection after DM or DBT and reduces interval cancers (cancers detected in the interval between recommended screening examinations), but it also produces substantial additional false-positive findings. MBI improves cancer detection with an effective radiation dose that is approximately fourfold that of DM or DBT but is still within accepted limits. MRI provides the greatest increase in cancer detection and reduces interval cancers and late-stage disease; abbreviated techniques will reduce cost and improve availability. CEM appears to offer performance similar to that of MRI, but further validation is needed. Dense breast notification will soon be a national standard; therefore, understanding the performance of mammography and supplemental modalities is necessary to optimize screening for women with dense breasts.

Objective The A6702 multisite trial confirmed that apparent diffusion coefficient (ADC) measures can improve breast MRI accuracy and reduce unnecessary biopsies, but also found that technical issues rendered many lesions non-evaluable on diffusion-weighted imaging (DWI). This secondary analysis investigated factors affecting lesion evaluability and impact on diagnostic performance. Methods The A6702 protocol was IRB-approved at 10 institutions; participants provided informed consent. In total, 103 women with 142 MRI-detected breast lesions (BI-RADS assessment category 3, 4, or 5) completed the study. DWI was acquired at 1.5T and 3T using a four b-value, echo-planar imaging sequence. Scans were reviewed for multiple quality factors (artifacts, signal-to-noise, misregistration, and fat suppression); lesions were considered non-evaluable if there was low confidence in ADC measurement. Associations of lesion evaluability with imaging and lesion characteristics were determined. Areas under the receiver operating characteristic curves (AUCs) were compared using bootstrapping. Results Thirty percent (42/142) of lesions were non-evaluable on DWI; 23% (32/142) with image quality issues, 7% (10/142) with conspicuity and/or localization issues. Misregistration was the only factor associated with non-evaluability (P = 0.001). Smaller (≤10 mm) lesions were more commonly non-evaluable than larger lesions (p Conclusion Image quality remains a technical challenge in breast DWI, particularly for smaller lesions. Protocol optimization and advanced acquisition and post-processing techniques would help to improve clinical utility.

Rationale and Objectives Use of preoperative breast MRI (pMRI) to evaluate ductal carcinoma in situ (DCIS) extent is controversial due to limited data on its impact on surgical management. We sought to evaluate the effect of pMRI on surgical management of women with core needle biopsy (CNB)-diagnosed pure DCIS at a multidisciplinary academic institution. Materials and Methods This retrospective study included all women with CNB-diagnosed DCIS (1/2004—12/2013) without prior ipsilateral breast cancer and who underwent surgery within 180 days of diagnosis. Patient features, number of CNBs and surgeries, and single successful breast conserving surgery (BCS) rate were compared between pMRI and no-pMRI cohorts. Number of surgeries and single BCS success rates were also compared to published US (SEER) and Danish National Registry data. Results Among the 373 women included, no clinical differences were identified between the pMRI ( n = 332) and no-pMRI ( n = 41) cohorts ( p > 0.05). The pMRI group experienced a higher additional CNB rate (30% vs. 7%, p = 0.002) but fewer total surgeries (mean = 1.2 vs. 1.5, p 0.001) than the no-pMRI group. Among the 245 women for whom BCS was attempted, the pMRI cohort underwent fewer mean surgeries (1.3 vs. 1.7, p 0.001) with a greater single successful BCS rate (77% vs. 43%, p 0.001). Compared to published data, women with pMRI who underwent BCS experienced fewer surgeries (difference (Δ) = −0.22 vs. −0.17, p 0.001) with a higher single successful BCS rate (Δ = +20% vs. +14%, p 0.001). Conclusion pMRI may improve surgical management of DCIS at multidisciplinary centers with breast cancer specialists.

PURPOSE: To examine the clinical value of multiband (MB) sensitivity encoding (SENSE)–accelerated diffusion-weighted imaging (DWI) for breast imaging by performing quantitative and qualitative comparisons with conventional diffusion-weighted echo-planar imaging, or conventional DWI (cDWI). MATERIALS AND METHODS: In this prospective study (ClinicalTrials.gov identifier NCT03607552), women with breast cancer were recruited from July 2018 to July 2019 to undergo additional MB SENSE DWI during clinical 3-T breast MRI examinations. The cDWI and MB SENSE DWI acquisitions were assessed both quantitatively and qualitatively. Regions of interest were defined for tumorous and normal tissue, and the tumor apparent diffusion coefficient (ADC), contrast-to-noise ratio (CNR), and signal index (SI) were calculated for both DWI methods. Three readers independently reviewed the two acquisitions side by side and provided relative image quality scores. Tumor ADC, CNR, and SI measures were compared between cDWI and MB SENSE DWI acquisitions by using a paired t test, and reader preferences were evaluated by using the sign test. RESULTS: The study included 38 women (median age, 48 years; range, 28–83 years). Overall agreement was good between cDWI and MB SENSE DWI tumor ADC measures (intraclass correlation coefficient, 0.87 [95% CI: 0.75, 0.94]), and no differences were evident in the ADC (median, 0.93 × 10(–3) mm(2)/sec vs 0.87 ×10(−3) mm(2)/sec; P = .50), CNR (2.2 vs 2.3; P = .17), or SI (9.2 vs 9.2; P = .23) measurements. The image quality of cDWI and MB SENSE DWI acquisitions were considered equal for 51% of images (58 of 114), whereas MB SENSE DWI was preferred more often than cDWI (37% [42 of 114] vs 12% [14 of 114]; P < .001). The preference for MB SENSE DWI was most often attributed to better fat suppression. CONCLUSION: MB SENSE can be used to accelerate breast DWI acquisition times without compromising the image quality or the fidelity of quantitative ADC measurements. Keywords: MR-Diffusion-weighted Imaging, Breast, Comparative Studies, Technology Assessment Clinical trial registration no. NCT03607552 © RSNA, 2022

Diffusion-weighted (DW) MRI is a rapid technique that measures the mobility of water molecules within tissue, reflecting the cellular microenvironment. At DW MRI, breast cancers typically exhibit reduced diffusivity and appear hyperintense to surrounding tissues. On the basis of this characteristic, DW MRI may offer an unenhanced method to detect breast cancer without the costs and safety concerns associated with dynamic contrast material–enhanced MRI, the current reference standard in the setting of high-risk screening. This application of DW MRI has not been widely explored but is particularly timely given the growing health concerns related to the long-term use of gadolinium-based contrast material. Moreover, increasing breast density notification legislation across the United States is raising awareness of the limitations of mammography in women with dense breasts, emphasizing the need for additional cost-effective supplemental screening examinations. Preliminary studies suggest unenhanced MRI with DW MRI may provide higher sensitivity than screening mammography for the detection of breast malignancies. Larger prospective multicenter trials are needed to validate single-center findings and assess the performance of DW MRI for generalized breast cancer screening. Standardization of DW MRI acquisition and interpretation is essential to ensure reliable sensitivity and specificity, and an optimal approach for screening using readily available techniques is proposed here. © RSNA, 2019 Online supplemental material is available for this article.

The value of breast MRI for DCIS detection and characterization remains highly debated. Though initially thought to be poor for DCIS detection, MRI is now well-established as the most superior imaging tool for DCIS detection and characterization. This is particularly true of high nuclear grade subtypes, possibly due MRI’s ability to not only reflect neovascularity but also basement membrane permeability. NMEs account for the majority of DCIS lesions identified on MRI and generally reflect a pathology growth pattern that extends along the milk ducts. Rarer presentations of DCIS as masses or foci may indicate a more indolent DCIS growth pattern that primarily expands rather than spreads along the milk ducts. DCIS exhibits variable semi-quantitative kinetic features, generally peaking later than invasive cancers and often resulting in medium initial phase and/or delayed phase persistent or plateau. The appearance of DCIS on diffusion weighted imaging and novel ultrafast sequences remains areas of active investigation. MRI is also more accurate than mammography at determining DCIS extent. Of nine studies published to date, eight concluded that MRI span is more accurate than mammographic span. However, the practical surgical benefit of this improved depiction of DCIS is less clear, with a meta-analysis and a recent systematic review showing no reduction in re-operation rate with preoperative MRI. Two more recent prospective multicenter trials (E4112 and IRCIS) and two newer retrospective studies have suggested that MRI may be associated with better surgical outcomes without increasing mastectomy rates. Still, there remains uncertainty in how MRI affects surgical management of DCIS. It is possible that MRI’s improved depiction of DCIS will only be of substantial clinical benefit when guiding future treatment de-escalation approaches to mitigate overtreatment, such as guiding multiple lumpectomies in lieu of mastectomies and/or omitting radiation therapy. Advances in artificial intelligence applied to radiological image features to develop and validate imaging biomarkers have created a major opportunity for MRI to assist with DCIS management by further illuminating lesion biology and heterogeneity. Prior studies have suggested that simple MRI features can correlate with basic pathologic features, such as nuclear grade, comedonecrosis, or ER positivity. MRI-based radiomic features have recently been shown to predict clinical outcomes such as ipsilateral breast recurrent for invasive cancers. Two pilots studies of DCIS and MRI radiomics demonstrated that quantitative parameters could predict nuclear grade and HER2 amplification and IBR. Preliminary data from the E4112 trial also has suggested that MRI radiomic features results in two distinct phenotypes that may have independent prognostic value. Future trials of DCIS should carefully standardize imaging approaches so that imaging markers can be developed and validated to improve DCIS management. Citation Format: Habib Rahbar. DCIS and MRI: Challenges translating MRI depiction of DCIS to improved clinical performance and future opportunities to optimize treatment [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA024.

BACKGROUND: There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). PURPOSE: To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. MATERIALS AND METHODS: Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results. DCIS MRI features and pathologic features from CNB and excision were recorded. Each woman without invasive upgrade of the index DCIS at WLE received a 12-gene DCIS score. MRI performance metrics were calculated. Associations of imaging features with invasive upgrade, dichotomized DCIS score (

Purpose To assess the influence of menstrual cycle timing on background parenchymal enhancement (BPE) and performance on screening breast magnetic resonance imaging (MRI) in premenopausal women at high risk for developing breast cancer. Methods After Institutional Review Board approval, all screening breast MRIs performed from January 2007 through November 2010 in premenopausal women in whom day from last menstrual period was recorded were identified. Prospectively recorded BPE levels and Breast Imaging Reporting and Data System MRI assessments were extracted from our database. Subject outcomes were determined by using biopsy, imaging follow-up, and linkage with the regional tumor registry (minimum 12-month follow-up). Associations of BPE levels (minimal/mild versus moderate/marked) with menstrual cycle phase (follicular [day 0–15] versus luteal [day 16–35]) and week (1, 2, 3, or 4) were compared. Differences in MRI performance metrics, including abnormal interpretation rate (AIR), positive biopsy rate (PBR), cancer yield, sensitivity, and specificity, were compared between menstrual cycle phase and menstrual cycle week. Results Three-hundred twenty examinations in 244 premenopausal women met inclusion criteria with nine cancers diagnosed. BPE levels were not associated with menstrual cycle phase or week (P > 0.05). MRI performance metrics (ie, AIR, PBR, cancer yield, sensitivity, or specificity) did not differ significantly based on menstrual cycle phase or menstrual cycle week (P > 0.05). Conclusions Obtaining screening breast MRI exams during specific phases or weeks of the menstrual cycle in premenopausal women does not reliably produce MRI examinations with lower BPE levels or improved performance.

The degree of normal fibroglandular tissue that enhances on breast MRI, known as background parenchymal enhancement (BPE), was initially described as an incidental finding that could affect interpretation performance. While BPE is now established to be a physiologic phenomenon that is affected by both endogenous and exogenous hormone levels, evidence supporting the notion that BPE frequently masks breast cancers is limited. However, compelling data have emerged to suggest BPE is an independent marker of breast cancer risk and breast cancer treatment outcomes. Specifically, multiple studies have shown that elevated BPE levels, measured qualitatively or quantitatively, are associated with a greater risk of developing breast cancer. Evidence also suggests that BPE could be a predictor of neoadjuvant breast cancer treatment response and overall breast cancer treatment outcomes. These discoveries come at a time when breast cancer screening and treatment have moved toward an increased emphasis on targeted and individualized approaches, of which the identification of imaging features that can predict cancer diagnosis and treatment response is an increasingly recognized component. Historically, researchers have primarily studied quantitative tumor imaging features in pursuit of clinically useful biomarkers. However, the need to segment less well-defined areas of normal tissue for quantitative BPE measurements presents its own unique challenges. Furthermore, there is no consensus on the optimal timing on dynamic contrast-enhanced MRI for BPE quantitation. This article comprehensively reviews BPE with a particular focus on its potential to increase precision approaches to breast cancer risk assessment, diagnosis, and treatment. It also describes areas of needed future research, such as the applicability of BPE to women at average risk, the biological underpinnings of BPE, and the standardization of BPE characterization. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:43-61.

Objectives The aims of this study were to identify optimal quantitative breast magnetic resonance imaging background parenchymal enhancement (BPE) parameters associated with breast cancer risk and compare performance to qualitative assessments. Methods Using a matched case-control cohort of 46 high-risk women who underwent screening magnetic resonance imaging (23 who developed breast cancer matched to 23 who did not), fibroglandular tissue area, BPE area, and intensity metrics (mean, SD, quartiles, skewness, and kurtosis) were quantitatively measured at varying enhancement thresholds. Optimal thresholds for discriminating between cancer and control cohorts were identified for each metric and performance summarized using area under the receiver operating characteristic curve. Results Women who developed breast cancer exhibited greater BPE area (adjusted P = 0.004) and higher intensity statistics (adjusted P 0.99) than did control subjects, with areas under the receiver operating characteristic curve ranging from 0.75 to 0.78 at optimized thresholds. Conclusions Elevated quantitative BPE parameters, related to both area and intensity of enhancement, are associated with breast cancer development.

Introduction: Triple negative breast cancer (TNBC) patients exhibit varied levels of response to neoadjuvant chemotherapy (NAC), with only 27-51% of patients achieving pathological complete response (pCR). This diverse response can be attributed in-part to heterogeneity of the tumor microenvironment, affecting therapeutic delivery and efficacy. Multiparametric magnetic resonance imaging (MRI) can be used to spatially resolve intratumoral heterogeneity into distinct tumor subregions, or habitats. We investigated whether MRI-derived tumor habitats identified prior to initiation of NAC were predictive of pathological response in TNBC patients. Methods: Women with stage II/III TNBC who received a pre-treatment (baseline) breast MRI and NAC at our institution (2012-2019) were retrospectively identified. Pathological response was determined at surgery, with pCR defined as no residual tumor within the breast or lymph nodes. Both diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI data were collected prior to initiation of NAC. The apparent diffusion coefficient (a measure of cell density) was calculated for each voxel from DW-MRI. Signal enhancement ratio, percent enhancement, and wash-out slope were calculated for each voxel from DCE-MRI, providing measures of vascularity. Hierarchical clustering of voxel data was used to identify tumor habitats, with each subregion labeled in terms of “high” or “low” vascularity and cellularity based on mean parameter values for the subregion. Tumor composition was quantified as percent tumor volume comprised by each habitat. Differences between pCR and non-pCR patients were assessed using Wilcoxon rank sum test, with p Results: 46 women with TNBC were retrospectively identified (median age: 48, range 31-77 yrs), of which 14 (30%) achieved pCR. No significant differences between pCR and non-pCR patients were observed in baseline tumor volume or longest diameter (p>0.05). Clustering analysis yielded four tumor habitats: low-vascularity low-cellularity (LV-LC), low-vascularity high-cellularity (LV-HC), high-vascularity low-cellularity (HV-LC), and high-vascularity high-cellularity (HV-HC). Patients who achieved pCR had significantly higher fraction of the HV-HC habitat at baseline (p=0.02). No significant differences were observed for other habitats. Discussion & Conclusion: Our findings suggest multiparametric MRI can identify physiologically-distinct tumor habitats prior to NAC, which are predictive of response. A higher fraction of HV-HC habitat was associated with pCR, potentially suggestive of increased therapeutic delivery/sensitivity. Clinical translation of this approach would enable more specific characterizations of tumor heterogeneity and prediction of response, which could aid in personalizing regimens for optimal outcomes. Citation Format: Anum S. Kazerouni, Laura C. Kennedy, Shaveta Vinayak, Suzanne Dintzis, Habib Rahbar, Savannah C. Partridge. Identification of pre-treatment tumor habitats for the prediction of neoadjuvant therapy response in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5980.

• Existing evidence suggests that preoperative breast MRI does not improve treatment outcomes for DCIS. • The quality of the available data used to answer this question is poor. • Quality randomized controlled trials are needed to definitively assess the benefits and harms of preoperative MRI in the setting of DCIS.

Ductal in-situ carcinoma (DCIS) is a non-invasive proliferation that lacks the ability to metastasize. Over the past four decades, DCIS diagnoses have increased ten-fold, with treatments nearly as aggressive as those for small low-grade invasive breast cancer. In this study, we evaluate the potential of identifying intrinsic imaging phenotype of DCIS using radiomic signatures from breast DCE-MRI. The rationale is that such phenotypes may capture aspects of the heterogeneity of DCIS that can aid in identifying indolent from aggressive disease to better stratify patients for improved disease management. An initial analysis was performed on eighty- two DCIS cases from the ECOG-ACRIN E4112 trial. The Cancer Phenomics Toolkit (CapTK) was used to extract a total of 95 3-D radiomic features from each primary lesion volume in pre-treatment, pre-operative breast DCE-MRI images. Features were first filtered for robustness across the heterogeneous clinical sites of DCE-MRI acquisition and features deemed non-robust (59) were discarded. Dimensionality reduction was performed with the remaining thirty-six features via principle component analysis (PCA). Unsupervised hierarchical clustering of the resulting five principal components (PCs) capturing 85% of the original feature variance was applied. Two significant intrinsic DCIS radiomic phenotypes were identified (p

Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation.To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS.A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy.Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery.Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation.Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one's breast (OR, 0.48; 95% CI, 0.31-0.72; P .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P .001).In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

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/mm(2)). 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/mm(2)) 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/mm(2); 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.

Objective To determine whether invasive lobular carcinoma (ILC) extent is more accurately depicted with preoperative MRI (pMRI) than conventional imaging (mammography and/or ultrasound). Methods After IRB approval, we retrospectively identified women with pMRIs (February 2005 to January 2014) to evaluate pure ILC excluding those with ipsilateral pMRI BI-RADS 4 or 5 findings or who had neoadjuvant chemotherapy. Agreement between imaging and pathology sizes was summarized using Bland-Altman plots, absolute and percent differences, and the intraclass correlation coefficient (ICC). Rates of underestimation and overestimation were evaluated and their associations with clinical features were explored. Results Among the 56 women included, pMRI demonstrated better agreement with pathology than conventional imaging by mean absolute difference (1.6 mm versus −7.8 mm, P < 0.001), percent difference (10.3% versus −16.4%, P < 0.001), and ICC (0.88 versus 0.61, P = 0.019). Conventional imaging more frequently underestimated ILC span than pMRI using a 5 mm difference threshold (24/56 (43%) versus 10/56 (18%), P < 0.001), a 25% threshold (19/53 (36%) versus 10/53 (19%), P = 0.035), and T category change (17/56 (30%) versus 7/56 (13%), P = 0.006). Imaging–pathology size concordance was greater for MRI-described solitary masses than other lesions for both MRI and conventional imaging (P < 0.05). Variability of conventional imaging was lower for patients ≥ the median age of 62 years than for younger patients (SD: 12 mm versus 22 mm, P = 0.012). Conclusion MRI depicts pure ILC more accurately than conventional imaging and may have particular value for younger women.

Screening mammography reduces breast cancer mortality; however, when used to examine women with dense breasts, its performance and resulting benefits are reduced. Increased breast density is an independent risk factor for breast cancer. Digital breast tomosynthesis (DBT), ultrasound (US), molecular breast imaging (MBI), MRI, and contrast-enhanced mammography (CEM) each have shown improved cancer detection in dense breasts when compared with 2D digital mammography (DM). DBT is the preferred mammographic technique for producing a simultaneous reduction in recalls (i.e., additional imaging). US further increases cancer detection after DM or DBT and reduces interval cancers (cancers detected in the interval between recommended screening examinations), but it also produces substantial additional false-positive findings. MBI improves cancer detection with an effective radiation dose that is approximately fourfold that of DM or DBT but is still within accepted limits. MRI provides the greatest increase in cancer detection and reduces interval cancers and late-stage disease; abbreviated techniques will reduce cost and improve availability. CEM appears to offer performance similar to that of MRI, but further validation is needed. Dense breast notification will soon be a national standard; therefore, understanding the performance of mammography and supplemental modalities is necessary to optimize screening for women with dense breasts.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Purpose Lobular neoplasia (LN) detected on breast core needle biopsy is frequently managed with surgical excision because of concern for undersampled malignancy. The authors performed a systematic review and meta-analysis to estimate the risk for upgrade to malignancy in the setting of imaging-concordant classic LN diagnosed on core biopsy. Methods PubMed and Embase were searched for original articles published from 1998 to 2020 that reported rates of upgrade to malignancy for classic LN, including atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (LCIS). Two reviewers extracted study data and assessed the following quality criteria: exclusion of variant LCIS, exclusion of imaging-discordant lesions, and outcome reporting for ≥70% of lesions. For studies meeting all criteria, pooled risks for upgrade to any malignancy (invasive carcinoma or ductal carcinoma in situ) and invasive malignancy for all LN, ALH, and LCIS were estimated using random-effects models. Results For 65 full-text articles included in the review, the risk for upgrade to any malignancy ranged from 0% to 45%. Among the 16 studies that met all quality criteria for the meta-analysis, pooled risks for upgrade to any malignancy were 3.1% (95% confidence interval [CI], 1.8%-5.2%) for all LN, 2.5% (95% CI, 1.6%-3.9%) for ALH, and 5.8% (95% CI, 2.9%-11.3%) for LCIS. Risks for upgrade to invasive malignancy were 1.3% (95% CI, 0.7%-2.4%) for all LN, 0.4% (95% CI, 0.0%-4.2%) for ALH, and 3.5% (95% CI, 2.0%-5.9%) for LCIS. Conclusions The risk for upgrade to malignancy for LN found on breast biopsy is low. Imaging surveillance can likely be offered as an alternative to surgical management for LN, particularly for ALH.

Angiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016–7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.

Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography.To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts.Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019.All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias.The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity.Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15).Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome.ClinicalTrials.gov Identifier: NCT02933489.

Rationale and Objectives On unenhanced diffusion-weighted imaging (DWI), computing or synthesizing high b-value images from lower b-value acquisitions can enhance breast cancer visibility. This study aimed to evaluate relative lesion conspicuity on computed versus acquired diffusion-weighted images and investigate clinical characteristics influencing optimal b-values. Materials and Methods Women with newly diagnosed breast cancer were prospectively enrolled and underwent 3T breast MRI with DWI. Lesion contrast-to-noise ratio (CNR) was measured across a range of b-values (0–2500 s/mm2) for computed and acquired DWI. Three readers independently compared lesion visibility between computed and acquired DWI and selected the optimal b-value. Computed versus acquired DWI was compared quantitatively based on CNR by paired t-test and qualitatively based on reader preference using a sign test. Optimal b-values by qualitative and quantitative assessment were compared by paired t-test, and associations with clinical characteristics were assessed by Wilcoxon rank sum test. Results The study included 30 women (median age, 48 years); 28 with invasive carcinoma, 2 DCIS. Lesion CNR was higher on acquired versus computed images (p = 0.018), while lesion visibility by reader assessment was not different (p = 0.36). Optimal b-values selected by readers (mean, b = 1411 ± 383 s/mm2) were slightly higher than those based on peak CNR (b = 1233 ± 463 s/mm2, p = 0.023), and were higher for younger (≤50 years) versus older women (p = 0.002) and dense versus nondense breasts (p = 0.015). Conclusion Lesion CNR on computed high b-value images was slightly reduced versus acquired images, but our study suggests that this did not significantly impact lesion visibility. Computing high b-value images offers extra flexibility to adjust b-value during interpretation.

Purpose To understand how breast radiologists perceive ductal carcinoma in situ (DCIS). Materials and Methods A 19-item survey was developed by the Society of Breast Imaging Patient Care and Delivery Committee and distributed to all Society of Breast Imaging members. The survey queried respondents’ demographics, knowledge of DCIS biology, language used to discuss a new diagnosis of DCIS, and perspectives on active surveillance for DCIS. Five-point Likert scales (1 = strongly disagree, 3 = neutral, 5 = strongly agree) were used. Results There were 536 responses for a response rate of 41%. There was agreement that DCIS is the primary driver of overdiagnosis in breast cancer screening (median 4), and respondents provided mean and median overdiagnosis estimates of 29.7% and 25% for low-grade DCIS as well as 4.2% and 0% for high-grade DCIS, respectively. Responses varied in how to describe DCIS but most often used the word “cancer” with a qualifier such as “early” (32%) or “pre-invasive” (25%). Respondents disagreed (median 2) with removing the word “carcinoma” from DCIS. Finally, there was agreement that current standard of care therapy for some forms of DCIS is overtreatment (median 4) and that active surveillance as an alternative management strategy should be studied (mean 4), but felt that ultrasound (median 4) and MRI (median 4) should be used to exclude women with occult invasive disease before active surveillance. Conclusions Breast radiologists’ opinions about DCIS biology, language, and active surveillance are not homogenous, but general trends exist that can be used to guide research, education, and advocacy efforts.

Purpose To investigate the visibility of mammographically occult breast cancers on diffusion-weighted MRI (DWI) versus ultrasound. Materials and methods Mammographically occult breast cancers (n = 60) initially detected on contrast-enhanced MRI that underwent pre-biopsy targeted ultrasound were retrospectively evaluated for visibility on DWI and ultrasound. Results More cancers were visible on DWI than ultrasound (78% vs. 63%; p = 0.049), with 32 (53%) visible on both and 7 (12%) not visible on either. Visibility differences were more significant in larger lesions (92% vs. 68%, p = 0.006). Conclusion DWI may detect more mammographically occult cancers than ultrasound, warranting further investigation as an alternative supplemental screening technique.

Purpose To investigate whether specific imaging features on breast magnetic resonance (MR) images are associated with ductal carcinoma in situ (DCIS) recurrence risk after definitive treatment. Materials and Methods Patients with DCIS who underwent preoperative dynamic contrast material-enhanced (DCE) MR imaging between 2004 and 2014 with ipsilateral recurrence more than 6 months after definitive surgical treatment were retrospectively identified. For each patient, a control subject with DCIS that did not recur was identified and matched on the basis of clinical, histopathologic, and treatment features known to affect recurrence risk. On DCE MR images, lesion characteristics (longest diameter, functional tumor volume [FTV], peak percentage enhancement [PE], peak signal enhancement ratio [SER], and washout fraction) and normal tissue features (background parenchymal enhancement [BPE] volume, mean BPE) were quantitatively measured. MR imaging features were compared between patients and control subjects by using the Wilcoxon signed-rank test, with adjustment for multiple comparisons. Results Of 415 subjects with DCIS who underwent preoperative MR imaging, 14 experienced recurrence and 11 had an identifiable matching control subject (final cohort, 11 patients and 11 control subjects). Median time to recurrence was 14 months, and median follow-up for control subjects was 102 months. When compared with matched control subjects, patients with DCIS recurrence exhibited significantly greater FTV (median, 9.3 cm3 vs 1.3 cm3, P = .01), lesion peak SER (median, 1.7 vs 1.2; P = .03), and mean BPE (median, 58.3% vs 41.1%; P = .02). Conclusion Quantitative lesion and normal breast tissue characteristics at preoperative MR imaging in women with newly diagnosed DCIS show promise for association with breast cancer recurrence after treatment. © RSNA, 2017.

Bonelli et al recently reported reduced humoral responses to the BNT162b2 mRNA vaccine in five patients on rituximab therapy; in two patients with repopulated B cells, a low-level Spike protein antibody response occurred, but three patients with no detectable B-cells had no measurable antibody response to the vaccine.1 Of great interest, they reported that interferon-γ T-cell responses to SARS-CoV-2 Spike peptides were present in all five patients, irrespective of the antibody response to the vaccine. It has been reported that patients on B-cell depleting therapy are at increased risk for hospitalisation and death from SARS-CoV-2 infection.2 In February 2021, the American College of Rheumatology (ACR) COVID-19 Taskforce published consensus guidelines regarding vaccine timing in immunosuppressed patients, despite the paucity of data available at that time on vaccine efficacy in patients on targeted B cell therapy.3 Moreover, the guidelines specifically …