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Objective To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR). Methods Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2− breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1−4, L1−4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response. Results Sixteen patients completed the trial. The %TC ranged 20%–80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7–0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to Conclusion In patients undergoing preoperative SABR treatment for ER/PR+ HER2− breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.

Breast cancer screening recommendations for transgender and gender nonconforming individuals are based on the sex assigned at birth, risk factors, and use of exogenous hormones. Insufficient evidence exists to determine whether transgender people undergoing hormone therapy have an overall lower, average, or higher risk of developing breast cancer compared to birth-sex controls. Furthermore, there are no longitudinal studies evaluating the efficacy of breast cancer screening in the transgender population. In the absence of definitive data, current evidence is based on data extrapolated from cisgender studies and a limited number of cohort studies and case reports published on the transgender community. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

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.

BACKGROUND. Higher categories of background parenchymal enhancement (BPE) increase breast cancer risk. However, current clinical BPE categorization is subjective. OBJECTIVE. Using a semiautomated segmentation algorithm, we calculated quantitative BPE measures and investigated the utility of individual features and feature pairs in significantly predicting subsequent breast cancer risk compared with radiologist-assigned BPE category. METHODS. In this retrospective case-control study, we identified 95 women at high risk of breast cancer but without a personal history of breast cancer who underwent breast MRI. Of these women, 19 subsequently developed breast cancer and were included as cases. Each case was age matched to four control patients (76 control patients total). Sociodemographic characteristics were compared between the cases and matched control patients using the Mann-Whitney U test. From each dynamic contrast-enhanced MRI examination, quantitative fibroglandular tissue and BPE measures were computed by averaging enhancing voxels above enhancement ratio thresholds (0–100%), totaling the enhancing volume above thresholds (BPE volume in cm(3)), and estimating the percentage of enhancing tissue above thresholds relative to total breast volume (BPE%) on each gadolinium-enhanced phase. For the 91 imaging features generated, we compared predictive performance using conditional logistic regression with 80:20 holdout cross validation and ROC curve analysis. ROC AUC was the figure of merit. Sensitivity, specificity, PPV, and NPV were also computed. All feature pairs were exhaustively searched to identify those with the highest AUC and Youden index. A DeLong test was used to compare predictive performance (AUCs). RESULTS. Women subsequently diagnosed with breast cancer were more likely to have mild, moderate, or marked BPE (odds ratio, 3.0; 95% CI, 0.9–10.0; p = .07). According to ROC curve analysis, a BPE category threshold greater than minimal resulted in a maximized AUC (0.62) in distinguishing cases from control patients. Compared with BPE category, the first gadolinium-enhanced (phase 1) BPE% at the 30% and 40% enhancement ratio thresholds yielded significantly higher AUC values of 0.85 (p = .0007) and 0.84 (p = .0004), respectively. Feature combinations showed similar AUC values with improved sensitivity. CONCLUSION. Preliminary data indicate that quantitative BPE measures may outperform radiologist-assigned category in breast cancer risk prediction. CLINICAL IMPACT. Future risk prediction models that incorporate quantitative measures warrant additional investigation.

ObjectiveAnalyze mammography quality and deficiencies, including variability in quality assessment among subspecialized breast radiologists, after implementing the Enhancing Quality Using the Inspection Program (EQUIP).MethodsAfter IRB approval, this single institution study retrospectively queried data prospectively entered into our automated reporting software after implementing EQUIP (October 2017–March 2019). Screening and diagnostic combination (digital mammography with tomosynthesis) mammograms were reviewed by seven breast radiologists. Quality was assessed as excellent, good, adequate, or problems found. Of those with problems found, the deficiency and corrective action were evaluated. The interpreting radiologist, EQUIP radiologist, and performing technologist were recorded. P values were calculated using Fisher exact test and chi-square analyses.ResultsOf 17 312 mammograms, 529 (3%) underwent EQUIP review. Of 43 (8%) with problems found, 23 (53%) did not include sufficient tissue, 9 (21%) had motion degradation, 3 (7%) had artifacts, 2 each (4.7% each) had the nipple not in profile or skin folds, and 4 (9%) were categorized as “other.” Nine (9/529, 1.7%) required recall for repeat imaging. The lead interpreting physician (LIP) was more likely to categorize mammograms as technically inadequate compared to other radiologists (P < 0.00001), and there were also statistically significant differences in how the remaining radiologists stratified cases (P < 0.00001) even when excluding the LIP.ConclusionInsufficient tissue was the most common problem identified in the EQUIP-reviewed mammograms with deficiencies. Significant variability was present among radiologist EQUIP designations. Ongoing review of clinical image quality with EQUIP allows for opportunities to provide corrective feedback.

Background: Tamoxifen uptake for risk reduction has remained low due to concerns about toxicity despite the efficacy and effectiveness data available. Studies of tamoxifen in the adjuvant and preventive setting have demonstrated that a decline in mammographic density (MD) of approximately 10% is consistently associated with better outcomes. Additionally, MD is one of the strongest independent predictors of breast cancer risk, apart from older age and BRCA1/2 mutation, among women. 4-hydroxytamoxifen topical gel (4-OHT) is a transdermal agent, shown in preliminary studies to be well-tolerated with similar decreases in Ki-67 to oral tamoxifen in presurgical DCIS studies and significant drug concentration in breast parenchyma but very low levels in the systemic circulation. This study examines changes in MD, a potential surrogate biomarker of prevention activity, as the primary endpoint for this one-year early-phase prevention trial using 4-OHT gel in high risk women. Trial design: Multicenter, randomized, placebo-controlled study of 4-OHT gel (2mg per breast) versus placebo in 152 women with heterogeneously or extremely dense breast tissue for 12 months using standard of care imaging, stratified by enrollment site and baseline breast density category. The primary objective of this study is to evaluate the change in percent MD (using Cumulus software) from baseline to the week 52 in women applying 4 mg (2mg per breast) 4-OHT gel versus placebo. The secondary objectives are to compare the Cumulus vs Volpara breast density measurement methods; evaluate the percentage of women with lowering of BIRADS density; estimate percentage of women with ≥ 10% absolute decrease in quantitative MD percentage; explore patient reported experience assessed by BESS questionnaire; laboratory toxicity assessment (F VIII, vWB factor, SHBG, lipid profile); compare the 2D vs. 3D breast density measurement methods to estimate percent change in mammographic breast density; evaluate serum measurements of parent drug and related metabolite levels and factors related to 4-OHT exposures, such as IGF pathway members, CRP, estradiol, and 4-OHT; collect tissue for biomarkers (among women undergoing optional pre- and post-treatment biopsies); examine the persistence in change of mammographic density one year after 4-OHT vs. placebo gel application has stopped. Eligibility criteria: Inclusion: Women age 40-69 years, or less than 40 years if 5-year breast cancer Gail risk is greater than/equal to 1.66%; heterogeneously or extremely dense breast tissue based on mammography. Exclusion: abnormal uterine bleeding, or prior diagnosis of endometrial hyperplasia, endometrial polyps, or endometrial cancer; prior use of SERMS and AIs, except for a maximum of 3 months and at least 12 months prior. Statistical methods: Considering an attrition rate of 15%, 128 evaluable women are expected to have both baseline and 52-week measurements of percent MD. With 64 women in each group, there is 80% power to detect a decrease of 6% in the 4-OHT group versus 2% in the placebo group with a common standard deviation of 8% using a two-sided t-test with a significance level of 0.05. Study accrual: Activated January 2018, as of July 1, 2019, 92 patients have been recruited and 79 were randomized. Citation Format: Banu K. Arun, Gretchen Gierach, Marion E Scoggins, Seema Khan, Sandra S Rao, Judy Garber, Sughra Raza, Nagi B. Kumar, Heather H Han, John Heine, Bethany Niell, Pavani Chalasani, Kimberly Fitzpatrick, Lee G Wilke, Amy Fowler, Heather C Beckwith, Carrie Mays, Saba Abutaseh, Lana Vornik, Oukseub Lee, Eileen Dimond, Marjorie Perloff, Diane Liu, J. Jack Lee, Powell Brown, Brandy Heckman-Stoddard. A randomized, double-blind, placebo-controlled study of 4-hydroxytamoxifen topical gel in women with mammographically dense breasts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-15-02.

Ductal carcinoma in situ (DCIS) is defined as a neoplastic proliferation of epithelial cells confined to the mammary ductal-lobular system. Although metastasis can occur at the very early stages of DCIS, the majority of metastatic breast cancers are believed to arise through a years-long process of somatic evolution within the physical constraints of milk ducts, characterized by the accumulation of heritable genetic and epigenetic changes. While these genetic alterations during breast carcinogenesis have been extensively studied without any outcome that can be used as a clinical biomarker, less attention has been paid to the microenvironmental conditions that select for these genotypes. We have demonstrated that evolving pre-cancerous hyperplastic breast cells are selected under physical tumor microenvironment conditions such as hypoxia, acidosis, and starvation. We have also shown that these harsh conditions select cells with more aggressive phenotypes. We have developed several markers for the adapted cells under these harsh conditions such as LAMP2b for acidosis or CA9 for hypoxia. We, therefore, hypothesize that the expression of physical microenvironment adaptation proteins (PMA) can differentiate indolent from aggressive DCIS and that this can be used for decision support. DCIS can be detected by screening mammography followed by a percutaneous Biopsy for pathologic confirmation, which may be followed by surgery +/- adjuvant therapy. Citation Format: Mehdi Damaghi, Zainab Raza, Rana Adil Farman, JiDong Bai, Joel Saltz, Bethany L. Niell. Physical tumor microenvironment biomarkers to predict DCIS progression, upstaging, and early metastasis [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 B018.

While breast imaging such as full-field digital mammography and digital breast tomosynthesis have helped to reduced breast cancer mortality, issues with low specificity exist resulting in unnecessary biopsies. The fundamental information used in diagnostic decisions are primarily based in lesion morphology. We explore a dual-energy compositional breast imaging technique known as three-compartment breast (3CB) to show how the addition of compositional information improves malignancy detection. Women who presented with Breast Imaging-Reporting and Data System (BI-RADS) diagnostic categories 4 or 5 and who were scheduled for breast biopsies were consecutively recruited for both standard mammography and 3CB imaging. Computer-aided detection (CAD) software was used to assign a morphology-based prediction of malignancy for all biopsied lesions. Compositional signatures for all lesions were calculated using 3CB imaging and a neural network evaluated CAD predictions with composition to predict a new probability of malignancy. CAD and neural network predictions were compared to the biopsy pathology. The addition of 3CB compositional information to CAD improves malignancy predictions resulting in an area under the receiver operating characteristic curve (AUC) of 0.81 (confidence interval (CI) of 0.74–0.88) on a held-out test set, while CAD software alone achieves an AUC of 0.69 (CI 0.60–0.78). We also identify that invasive breast cancers have a unique compositional signature characterized by reduced lipid content and increased water and protein content when compared to surrounding tissues. Clinically, 3CB may potentially provide increased accuracy in predicting malignancy and a feasible avenue to explore compositional breast imaging biomarkers. Leong et al. use a dual-energy mammography technique termed three-compartment breast imaging to study breast composition and detect malignant lesions. Combining compositional information with morphology-based computer-aided diagnosis improves breast cancer detection. Breast cancers are detected by mammography. This study explored the use of a particular kind of mammography technique to obtain information about the composition of cancerous and non-cancerous breast tissue. This technique provided measures of lipid (fat), water, and protein content in addition to shape characteristics provided from standard mammography. Adding information about the composition of the tissue to its shape characteristics resulted in an increased ability to distinguish invasive cancerous tissue from unaffected surroundings. Invasive breast cancer tissues were also found to exhibit lower lipid, higher protein and higher water content when compared to other non-invasive, non-cancerous breast tissues in which cancer was suspected. Our findings highlight the added value of including the composition of breast tissue when deciding if biopsy of the suspicious tissue is warranted.

ObjectiveThe purpose of this study is to evaluate the utility of routine axillary ultrasound surveillance in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection.MethodsA retrospective review of our institutional database identified axillary and breast ultrasound examinations performed between February 1, 2011, and August 31, 2017, in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection. From the electronic medical record, patient demographics, imaging data, pathology results, and surgical reports were extracted. Positive predictive values (PPVs) 2 and 3 and cancer detection rate (CDR) were calculated with exact 95% confidence intervals (CIs).ResultsAn average of 2.1 surveillance examinations was performed in 77 unique patients, yielding 160 total examinations. For 7 patients, 7 biopsies were recommended, and 5 biopsies were performed. No malignancy was diagnosed, yielding a PPV2 of 0% (0/7) (95% CI = 0% to 35%); PPV3 of 0% (0/5) (95% CI = 0% to 45%), and CDR of zero per 1000 (0/160) examinations (95% CI = 0 to 19).ConclusionGiven the low frequency of axillary recurrence, routine axillary surveillance ultrasound in women with T1 or T2 breast cancers and 1 to 2 positive lymph nodes would be expected to have a low incremental CDR compared to clinical evaluation alone. Axillary surveillance ultrasound should not be routinely recommended or performed.

Background: Patients achieving a pathologic complete response (pCR) following neoadjuvant therapy have significantly improved event-free survival relative to those who do not; and pCR is an FDA-accepted endpoint to support accelerated approval of novel agents/combinations in the neoadjuvant treatment of high risk early stage breast cancer. Previous studies have shown that recurrence risk increased with increasing burden of residual disease (as assessed by the RCB index). As well, these studies suggest that patients with minimum residual disease (RCB-I class) also have favorable outcomes (comparable to those achieving a pCR) within high risk tumor subtypes. In this study, we assess whether integrating RCB with MRI functional tumor volume (FTV), which in itself is prognostic, can improve prediction of distant recurrence free survival (DRFS); and identify a subset of patients with minimal residual disease with comparable DRFS as those who achieved a pCR. Imaging tools can then be used to identify the subset that will do well early and guide the timing of surgical therapy. Method: We performed a pooled analysis of 596 patients from the I-SPY2 TRIAL with RCB, pre-surgical MRI FTV data and known follow-up (median 2.5 years). We first assessed whether FTV predicts residual disease (pCR or pCR/RCB-I) using ROC analysis. We applied a power transformation to normalize the pre-surgical FTV distribution; and assessed its association with DRFS using a bi-variate Cox proportional hazard model adjusting for HR/HER2 subtype. We also fitted a bivariate Cox model of RCB index adjusting for subtype; and assessed whether adding pre-surgical FTV to this model further improves association with DRFS using a likelihood ratio (LR) test. For the Cox modeling, penalized splines approximation of the transformed FTV and RCB index with 2 degrees of freedom was used to allow for non-linear effects of FTV and RCB on DRFS. Result: Pre-surgical MRI FTV is significantly associated with DRFS (Wald p Conclusion: Pre-surgical MRI FTV is effective at predicting minimal residual disease (RCB0/I) in the I-SPY 2 TRIAL. Despite the association between FTV and RCB, FTV appears to provide independent added prognostic value (to RCB and subtype), suggesting that integrating MRI volume measures and RCB into a composite predictor may improve DRFS prediction. Citation Format: Hylton NM, Symmans WF, Yau C, Li W, Hatzis C, Isaacs C, Albain KS, Chen Y-Y, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal I, Tawfik O, Grasso LeBeau L, Sahoo S, Vinh T, Yang S, Adams A, Chien AJ, Ferero-Torres A, Stringer-Reasor E, Wallace A, Boughey JC, Ellis ED, Elias AD, Lang JE, Lu J, Han HS, Clark AS, Korde L, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Wood WC, Park JW, Liu MC, Olopade O, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, Haugen PK, van't Veer LJ, Perlmutter J, Melisko ME, Wilson A, Peterson G, Asare AL, Buxton MB, Paoloni M, Clennell JL, Hirst GL, Singhrao R, Steeg K, Matthews JB, Sanil A, Berry SM, Abe H, Wolverton D, Crane EP, Ward KA, Nelson M, Niell BL, Oh K, Brandt KR, Bang DH, Ojeda-Fournier H, Eghtedari M, Sheth PA, Bernreuter WK, Umphrey H, Rosen MA, Dogan B, Yang W, Joe B, I-SPY 2 TRIAL Consortium, Yee D, Pusztai L, DeMichele A, Asare SM, Berry DA, Esserman LJ. Refining neoadjuvant predictors of three year distant metastasis free survival: Integrating volume change as measured by MRI with residual cancer burden [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-03.

OBJECTIVE. Supplemental screening breast MRI is recommended for women with an estimated lifetime risk of breast cancer of greater than 20-25%. The performance of risk prediction models varies for each individual and across groups of women. The present study investigates the concordance of three breast cancer risk prediction models among women presenting for screening mammography. SUBJECTS AND METHODS. In this prospective study, we calculated the estimated lifetime risk of breast cancer using the modified Gail, Tyrer-Cuzick version 7, and BRCAPRO models for each woman who presented for screening mammography. Per American Cancer Society guidelines, for each woman the risk was categorized as less than 20% or 20% or greater as well as less than 25% or 25% or greater with use of each model. Venn diagrams were constructed to evaluate concordance across models. The McNemar test was used to test differences in risk group allocations between models, with p ≤ .05 considered to denote statistical significance. RESULTS. Of 3503 screening mammography patients who underwent risk stratification, 3219 (91.9%) were eligible for risk estimation using all three models. Using at least one model, 440 (13.7%) women had a lifetime risk of 20% or greater, including 390 women (12.1%) according to the Tyrer-Cuzick version 7 model, 18 (0.6%) according to the BRCAPRO model, and 141 (4.4%) according to the modified Gail model. Six women (0.2%) had a risk of 20% or greater according to all three models. Women were significantly more likely to be classified as having a high lifetime breast cancer risk by the Tyrer-Cuzick version 7 model compared with the modified Gail model, with thresholds of 20% or greater (odds ratio, 6.4; 95% CI, 4.7-8.7) or 25% or greater (odds ratio, 7.4; 95% CI, 4.7-11.9) used for both models. CONCLUSION. To identify women with a high lifetime breast cancer risk, practices should use estimates of lifetime breast cancer risk derived from multiple risk prediction models.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Screening mammography aims to identify small, node-negative breast cancers when they are still curable while maintaining an acceptable range of false-positive recalls and biopsies. The mammography audit is a powerful tool to help radiologists understand their performance with respect to that goal. This article defines audit terms and describes how to use collected and derived data to perform a mammography audit. Accepted benchmarks are discussed as well as their applicability to radiologists and breast imaging practices in the United States. Special considerations regarding volumes and radiologist characteristics are explored, because these factors may affect audit results.

Mastectomy may be performed to treat breast cancer or as a prophylactic approach in women with a high risk of developing breast cancer. In addition, mastectomies may be performed with or without reconstruction. Reconstruction approaches differ and may be autologous, involving a transfer of tissue (skin, subcutaneous fat, and muscle) from other parts of the body to the chest wall. Reconstruction may also involve implants. Implant reconstruction may occur as a single procedure or as multistep procedures with initial use of an adjustable tissue expander allowing the mastectomy tissues to be stretched without compromising blood supply. Ultimately, a full-volume implant will be placed. Reconstructions with a combination of autologous and implant reconstruction may also be performed. Other techniques such as autologous fat grafting may be used to refine both implant and flap-based reconstruction. This review of imaging in the setting of mastectomy with or without reconstruction summarizes the literature and makes recommendations based on available evidence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation.Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.5 Gy in 3 fractions), follow-up MRI 5 to 6 weeks post-SABR, and lumpectomy. Tumor size and BI-RADS descriptors on pre and post-SABR breast MRIs were compared to determine correlation with surgical specimen % tumor cellularity (%TC). Reported MRI tumor dimensions were used to calculate percent cubic volume remaining (%VR). Partial MRI response was defined as a BI-RADs descriptor change or %VR ≤ 70%, while partial pathologic response (pPR) was defined as %TC ≤ 70%.Nineteen patients completed the trial, and %TC ranged 10% to 80%. For BI-RADS descriptor analysis, 12 of 19 (63%) showed change in lesion or kinetic enhancement descriptors post-SABR. This was associated with lower %TC (29% vs. 47%, P = .042). BI-RADS descriptor change analysis also demonstrated high PPV (100%) and specificity (100%) for predicting pPR to treatment (sensitivity 71%, accuracy 74%), but low NPV (29%). MRI %VR demonstrated strong linear correlation with %TC (R = 0.70, P.001, Pearson's Correlation) and high accuracy (89%) for predicting pPR (sensitivity 88%, specificity 100%, PPV 100%, and NPV 50%).Evaluating breast cancer response on MRI using %VR after pre-operative SABR treatment can help identify patients benefiting the most from neoadjuvant radiation treatment of their ER/PR+ HER2- tumors, a group in which pCR to neoadjuvant therapy is rare.

Purpose The Enhancing Quality Using the Inspection Program (EQUIP) initiative was launched to improve clinical image quality. The purpose of this study was to determine if the implementation of the EQUIP reporting system resulted in an increased number of extra views performed at the technologists' discretion during screening mammography. Materials and methods Following IRB approval at a single comprehensive cancer center, patients who underwent screening mammography with combination full-field digital mammography plus digital breast tomosynthesis during a 6-month period before (January 2017 to June 2017) and after (January 2018 to June 2018) EQUIP implementation were identified. For each patient, both screening mammograms were retrospectively reviewed by 1 of 3 subspecialized breast radiologists (3–10 years of experience). The following data were recorded: demographics, breast density, surgical history, technologist, number and type of extra views, final BI-RADS assessment, radiologist-assigned indication for the view, and radiologist-assigned necessity of the view. McNemar's test for paired data was computed with p value of Results Of 820 patients, 370 (45%) had additional views in 2018 compared to 317 (39%) in 2017. After EQUIP, patients were 38% more likely to have additional views (OR = 1.38, 95% CI = 1.11–1.73). The total number of additional views in 2018 was 636 compared to 530 in 2017 (20% increase). Among patients with extra views in both years, the number of additional views per patient did not significantly increase post EQUIP implementation (OR = 1.18, 95% CI = 0.73–1.92). The most common extra view was exaggerated craniocaudal lateral, and the most common reason cited by the reviewing radiologist was lateral fibroglandular tissue at the edge of the images. Most of the extra views performed in 2018 were not performed in 2017 and over half were deemed unnecessary. Eight of eleven technologists demonstrated an increased frequency of screening mammograms with extra views performed post EQUIP. Conclusion Following EQUIP implementation, screening mammography patients were significantly more likely to have extra views performed at the technologists' discretion. Our findings emphasize the importance of ongoing technologist education and radiologist feedback.

Purpose: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). Patients and Methods: Patients with stage II–III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3–5 adverse events due to TVEC during first 5 weeks. Results: Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%). Conclusions: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.

Our purpose was to determine if the lipid, water, and protein lesion composition (3CB), combined with computer-aided detection (CAD) had higher biopsy malignancy specificity than CAD alone. High and low-kVp full-field digital 3CB mammograms were acquired on women with suspicious mammographic lesions (BIRADS 4) and that were to undergo biopsy. Radiologists delineated 673 lesions (98 invasive ductal cancers (IDC), 60 ductal carcinomas in situ (DCIS), 103 fibroadenomata (FA), and 412 benign (BN)) on the diagnostic mammograms using the pathology report to confirm location. The diagnostic mammograms were processed by iCAD SecondLook software using its most sensitive setting to create to further delineations and probabilities of malignancy. The iCAD delineated a total of 375 annotation agreeing regions that were classified as either masses or calcification cluster. The 3CB algorithm produced lipid, water, and protein thickness maps for all ROIs and peripheral rings from which 84 compositional input features were derived. A neural network (3CBNN) was trained with cross-validation on 80% of the data to predict the lesion type. Biopsy pathology served as the gold standard outcome. IDC and DCIS predicted probabilities were summed together to obtain a probability of malignancy which was evaluated against the iCAD probabilities using the area under the ROC curves. On a holdout test set, 20% of the data, the iCAD's output alone had an AUC of 0.61 while the 3CBNN’s AUC was 0.73. We conclude that compositional information provided by the 3CB algorithm contains important diagnostic information that can increase specificity of CAD software.

Breast imaging during pregnancy and lactation is challenging due to unique physiologic and structural breast changes that increase the difficulty of clinical and radiological evaluation. Pregnancy-associated breast cancer (PABC) is increasing as more women delay child bearing into the fourth decade of life, and imaging of clinical symptoms should not be delayed. PABC may present as a palpable lump, nipple discharge, diffuse breast enlargement, focal pain, or milk rejection. Breast imaging during lactation is very similar to breast imaging in women who are not breast feeding. However, breast imaging during pregnancy is modified to balance both maternal and fetal well-being; and there is a limited role for advanced breast imaging techniques in pregnant women. Mammography is safe during pregnancy and breast cancer screening should be tailored to patient age and breast cancer risk. Diagnostic breast imaging during pregnancy should be obtained to evaluate clinical symptoms and for loco-regional staging of newly diagnosed PABC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Objective The purpose of our study was to determine the frequency of successful SAVI SCOUT® localizations, to identify the factors contributing to unsuccessful procedures, and to provide a problem-solving algorithm to address those factors. Subjects and methods This retrospective study was performed following IRB approval. We included all consecutive patients with SCOUT® reflector placement performed at a single tertiary-care cancer center. Each case was reviewed and the following data were recorded: patient age, breast density, localization target, imaging modality used for guidance, post procedure mammogram reflector to skin and reflector to target distances, presence of the reflector in the specimen radiograph, excisional biopsy pathology and any procedure complications. Results In 129 women, 152 SAVI SCOUT® reflectors were placed. Most patients had only 1 reflector placed, but 19 (15%) women had multiple reflectors placed for the purposes of bracketing, multiple excisions in 1 breast, bilateral excisions, or any combination thereof. The most common target was a mass (65%) and the most common modality for guidance was ultrasound (73%). SAVI SCOUT® localization was successful in 97%of reflectors, including 89% of reflectors targeting axillary lymph nodes. The most common failure encountered was the inability to obtain a signal in the radiology suite, due to (1) excessive target depth for the radiology suite handpiece and console, (2) obscuration by a hematoma, or (3) faulty reflector. No post-operative complications occurred. Conclusion The SAVI SCOUT® surgical guidance system is an accurate and reliable method for localization of non-palpable breast lesions, bracketing, and axillary lymph nodes.

Background Women with breast imaging often seek second opinions at tertiary care centers. Our study measures the frequency of discrepancy between initial and second opinion breast imaging recommendations and evaluates the impact on patient management. Materials and Methods A retrospective chart review was conducted on 504 consecutive patients with second opinion breast radiology interpretations performed by 6 sub-specialized breast radiologists at a dedicated cancer center from January 1, 2014 through September 1, 2014. Outside imaging reports were compared with second opinion reports to categorize discrepancies. Interpretations were considered discrepant in cases with Breast Imaging Reporting and Data System (BI-RADS) category changes, recommendation for additional imaging, or identification of previously undiagnosed additional extent of disease greater than 5 cm. The frequencies of discrepancy, alterations in surgical management, and incremental cancer detection were measured. Statistical analysis of associated factors was performed with the Fisher exact test, with a P-value Results Second opinion evaluation discrepancies were seen in 287 (57%) patients and resulted in percutaneous image-guided biopsies in 92 (18%). Forty-five additional sites of cancer were biopsy-detected in 41 (8%) patients, including 20 breast malignancies and 25 axillary metastases. Another 9 biopsies yielded high-risk pathology. Second opinion interpretations altered surgical management in 66 (13%) patients. Factors associated with increased discrepancy frequency were cancer diagnosis at presentation (P = .004), dense breasts (P = .005), and the absence of prior studies for comparison (P = .007). Conclusion Although additional imaging and resources are required, second opinion radiology review by subspecialized breast radiologists increases cancer detection and results in clinically relevant changes in patient management.

Breast implant imaging varies depending on patient age, implant type, and symptoms. For asymptomatic patients (any age, any implant), imaging is not recommended. Rupture of saline implants is often clinically evident, as the saline is resorbed and there is a change in breast contour. With saline implants and equivocal clinical findings, ultrasound (US) is the examination of choice for patients less than 30 years of age, either mammography/digital breast tomosynthesis or US may be used for those 30 to 39 years of age, and mammography/digital breast tomosynthesis is used for those 40 years and older. For patients with suspected silicone implant complication, MRI without contrast or US is used for those less than 30 years of age; MRI without contrast, mammography/digital breast tomosynthesis, or US may be used for those 30 to 39 years of age; and MRI without contrast or mammography/digital breast tomosynthesis is used for those 40 years and older. Patients with unexplained axillary adenopathy and silicone implants (current or prior) are evaluated with axillary US. For patients 30 years and older, mammography/digital breast tomosynthesis is performed in conjunction with US. Last, patients with suspected breast implant-associated anaplastic large-cell lymphoma are first evaluated with US, regardless of age or implant type. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background: The host anti-tumor immune response plays an important role in determining natural history and therapy response for early stage breast cancer. Tumors with high levels of lymphocytic infiltration appear to have a superior prognosis and response rate to neoadjuvant chemotherapy. However, these tumors are in the minority so methods to enhance tumor lymphocyte infiltration should be identified. The oncolytic virus, talimogene laherparpvec (TVEC) is a genetically modified HSV1 virus which selectively replicates in transformed cells while sparing normal tissue. This leads to lysis of infected tumor cells along with co-expression of GM-CSF to elicit an enhanced anti-tumor immune response. Prior data has shown TVEC can be safely combined with chemotherapy in other indications, so we launched an investigator initiated study to determine the safety and efficacy of combining TVEC with neoadjuvant dose dense chemotherapy in stage II-III TNBC. Study design: The study is a phase 1 (2 dose levels of TVEC, 3+3 design) and phase 2 single arm Simon two stage combination trial. Primary endpoints of phase 1 is safety of intratumoral TVEC (DL1=106 PFU x 5 injections, DL2=106 PFU x 1 then 108 PFU x 4 injections) administered q2-3 weeks concurrently with weekly paclitaxel followed by standard dose dense AC x 4 and local therapy as indicated. Phase 2 primary endpoint is pCR rate of the study treatment, secondary endpoints include DFS, OS, immune correlates in resected tumor specimens. Eligibility criteria includes females >17 years old, newly diagnosed T2-3N0-3 TNBC, adequate organ function, primary tumor amenable to injection with TVEC, no immunosuppressive or autoimmune conditions, no inflammatory or bilateral/multifocal disease. Sample size is up to 49 patients (12 phase 1, 37 phase 2) with 80% power to detect increase in pCR rate from 30% to 50% with one sided p=.1 in phase 2. Study status: This novel Amgen supported investigator initiated study activated to accrual 3/2017 and first patient on study was on 5/2017. The study is currently open only at the Moffitt Cancer Center. Target study completion date 8/2021. (NCT02779855) Citation Format: Soliman HH, Hogue D, Han H, Lee C, Ismail-Khan R, Khong H, Niell B, Czerniecki B. Phase 1/2 trial of the oncolytic virus, talimogene laherparpvec, in combination with neoadjuvant chemotherapy in stage II/III triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-07-01.

Patients with locally advanced invasive breast cancers are often treated with neoadjuvant chemotherapy prior to definitive surgical intervention. The primary aims of this approach are to: 1) reduce tumor burden thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in-vivo tumor response. Accurate radiological assessment permits optimal management and planning in this population. However, assessment of tumor size and response to treatment can vary depending on the modality used, the measurement technique (such as single longest diameter, 3-D measurements, or calculated tumor volume), and varied response of different tumor subtypes to neoadjuvant chemotherapy (such as concentric shrinkage or tumor fragmentation). As discussed in further detail, digital mammography, digital breast tomosynthesis, US and MRI represent the key modalities with potential to help guide patient management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Appropriate imaging evaluation of nipple discharge depends the nature of the discharge. Imaging is not indicated for women with physiologic nipple discharge. For evaluation of pathologic nipple discharge, multiple breast imaging modalities are rated for evidence-based appropriateness under various scenarios. For women age 40 or older, mammography or digital breast tomosynthesis (DBT) should be the initial examination. Ultrasound is usually added as a complementary examination, with some exceptions. For women age 30 to 39, either mammogram or ultrasound may be used as the initial examination on the basis of institutional preference. For women age 30 or younger, ultrasound should be the initial examination, with mammography/DBT added when ultrasound shows suspicious findings or if the patient is predisposed to developing breast cancer. For men age 25 or older, mammography/DBT should be performed initially, with ultrasound added as indicated, given the high incidence of breast cancer in men with pathologic nipple discharge. Although MRI and ductography are not usually appropriate as initial examinations, each may be useful when the initial standard imaging evaluation is negative. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The purpose of this study was to determine the frequency and associated risk factors contributing to immediate tissue marker migration in patients undergoing MRI-guided breast biopsy and to evaluate how often tissue marker migration altered clinical management. Between July 2010 and May 2015, we retrospectively reviewed all MRI-guided breast biopsies at our institution for tissue marker migration. Migration was defined as final position of the tissue marker >10 mm from the target site based on the expected location of the MRI finding on postprocedure mammogram. Factors associated with migration were analyzed using Fisher's exact test and Chi-squared test, with P < .05 considered statistically significant. A total of 278 patients underwent 298 MRI-guided biopsies. Migration occurred in 42/298 biopsies (14%). Almost entirely fat fibroglandular tissue was identified as an independent risk factor for tissue marker migration, occurring in 6/16 (38%), compared to 36/262 (14%) for the other fibroglandular tissue categories (P = .03). Biopsy target size was significantly associated with clip migration, occurring in 25/114 (22%) lesions

The objective of our study was to compare the supplemental cancer yield and performance of breast MRI in women at higher-than-average risk for breast cancer after negative 2D full-field digital mammography (FFDM) or negative digital breast tomosynthesis (DBT).Retrospective review identified 4418 screening breast MRI examinations: 2291 were performed from January 2010 through January 2012 of patients with a negative FFDM examination in the 12 months before MRI (FFDM group), and 2127 were performed from January 2013 through January 2015 of patients with a negative DBT examination in the 12 months before MRI (DBT group). Screening indications included genetic predisposition, personal history of breast cancer or high-risk lesion, prior chest irradiation, family history, or other risk factors conferring a lifetime risk of greater than 20%. Supplemental cancer detection rate (CDR), abnormal interpretation rate (AIR), and positive predictive values (PPVs) were estimated with 95% exact CIs. Logistic regression analysis, adjusting for differences in patient demographics, was used to compare metrics.There was no significant difference in the CDR of MRI in the FFDM group versus the DBT group (11 vs 16 cancers per 1000 examinations, respectively; odds ratio, 1.4; 95% CI, 0.4-1.2; p = 0.23). The AIR, PPV1, PPV2, and PPV3 were 7.4%, 15%, 23%, and 28% for the FFDM group and 7.3%, 22%, 33%, and 35% for the DBT group, with no statistical differences. Of the cancers detected in both groups, the majority were invasive, less than 1 cm, and node-negative.In women at higher-than-average risk of breast cancer screened with DBT, the supplemental CDR of MRI is similar to that of MRI after FFDM screening, with most cancers being invasive, subcentimeter, and node-negative.

PURPOSE: To investigate the combination of mammography radiomics and quantitative three-compartment breast (3CB) image analysis of dual-energy mammography to limit unnecessary benign breast biopsies. MATERIALS AND METHODS: For this prospective study, dual-energy craniocaudal and mediolateral oblique mammograms were obtained immediately before biopsy in 109 women (mean age, 51 years; range, 31–85 years) with Breast Imaging Reporting and Data System category 4 or 5 breast masses (35 invasive cancers, 74 benign) from 2013 through 2017. The three quantitative compartments of water, lipid, and protein thickness at each pixel were calculated from the attenuation at high and low energy by using a within-image phantom. Masses were automatically segmented and features were extracted from the low-energy mammograms and the quantitative compartment images. Tenfold cross-validations using a linear discriminant classifier with predefined feature signatures helped differentiate between malignant and benign masses by means of (a) water-lipid-protein composition images alone, (b) mammography radiomics alone, and (c) a combined image analysis of both. Positive predictive value of biopsy performed (PPV(3)) at maximum sensitivity was the primary performance metric, and results were compared with those for conventional diagnostic digital mammography. RESULTS: The PPV(3) for conventional diagnostic digital mammography in our data set was 32.1% (35 of 109; 95% confidence interval [CI]: 23.9%, 41.3%), with a sensitivity of 100%. In comparison, combined mammography radiomics plus quantitative 3CB image analysis had PPV(3) of 49% (34 of 70; 95% CI: 36.5%, 58.9%; P < .001), with a sensitivity of 97% (34 of 35; 95% CI: 90.3%, 100%; P < .001) and 35.8% (39 of 109) fewer total biopsies (P < .001). CONCLUSION: Quantitative three-compartment breast image analysis of breast masses combined with mammography radiomics has the potential to reduce unnecessary breast biopsies. © RSNA, 2018 Online supplemental material is available for this article.

578 Background: TVEC is a modified oncolytic herpes simplex 1 (HSV1) virus currently FDA approved for the treatment of unresectable cutaneous and nodal melanoma. TVEC is designed to preferentially lyse tumor cells over normal tissue to release tumor associated antigens, produces GM-CSF to activate dendritic cells, and stimulates T cells to infiltrate the tumor (TILs). TILs in breast cancer are associated with better response to neoadjuvant chemotherapy (NAC), so we hypothesized that intratumoral TVEC may enhance response to NAC. We report results of a phase 2 trial combining NAC with TVEC in stage 2-3 TNBC. Methods: Stage II-III TNBC pts (N = 37) were to be enrolled into a single arm, optimal Simon 2 stage phase 2 trial with TVEC (10^6 PFU 1st dose then 10^8 PFU x 4 doses) weeks 1,4,6,8,10 + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone given preoperatively. Primary endpoint was residual cancer burden 0 rate (RCB0). Trial meets primary endpoint with ≥15 RCB0 responses out of 37 evaluable pts, assuming p1 = 45% vs. p0 = 30% with one sided type I error rate at 0.10 and power at 70%. Results: Forty pts were enrolled at Moffitt (5/2018 – 4/2020) and evaluable for safety with 3 pts non-evaluable for efficacy due to incomplete treatment. Study demographics: median age 49 (27-66), 67.5% White, 10% Black, 15% Hispanic, clinical stage II 83% and III 17%, node + 42%. The RCB0 rate = 16/37 (43%, 95% CI 27-61%) and additional 9 pts with RCB-1 (RCB0/1 rate 68%, 95% CI 50-82%). Toxicities did not differ significantly from expected NAC toxicities except for increased brief G1-2 fevers, chills, injection site pains. Four pts had G2-3 thromboembolic events (10%) slightly greater than expected 6% rate on NAC. Conclusions: Addition of TVEC to NAC increased RCB0 rates with manageable toxicities and warrants additional investigation in TNBC. Immune correlates and updated survival data will be presented at the meeting. Clinical trial information: NCT02779855.

Background: In an adaptive randomized trial, when new treatment combinations are being tested, it is important to be able to identify patients who are progressing on treatment so that they can be changed to a different therapeutic regimen. We know that even within the molecularly high risk patients in I-SPY 2, there is considerable variation in biology. In this study, we will present results of using MRI-calculated functional tumor volume (FTV) to identify tumor progression for each breast cancer subtype. Methods: Patients (n=990) enrolled in the I-SPY 2 TRIAL who were randomized to the graduated experimental drug arms or controls from 2010 to 2016 were analyzed. Four MRI exams were performed for each patient: pre-NAC (T0), after 3 weeks of NAC (T1), between regimens (T2), and post-NAC (T3). Functional tumor volume (FTV) was calculated at each exam by summing voxels meeting enhancement thresholds. Tumor progression at T1, T2 or T3 was identified by a positive FTV change relative to T0. Visual inspection was used to exclude false progression due to strong background parenchymal enhancement post-contrast, prominent vessels, motion, or insufficient image quality. pCR was defined as no invasive disease in the breast and lymph nodes. Negative predictive value for pCR was defined as:NPV=number of true non-pCRs / number of patients with MRI assessed tumor progressions, where “true non-pCRs” referred to patients who were non-pCRs at surgery and were assessed as progressors by MRI. The analysis was performed in the full cohort and in sub-cohorts defined by HR and HER2 statuses. Results: Out of 990 patients, 878 had pCR outcome data (pCR or non-pCR, pCR rate = 35%). Total and non-pCR numbers for each subtype, number of patients with tumor progression assessed by MRI at T1, T2, and T3, and NPVs, are shown in Table 1. In the full cohort, the NPV increased consistently over treatment, from T1 (NPV=83%) to T2 (93%), and to T3 (100%). The HER2+ cancer subtypes showed fewer MRI-assessed tumor progressions than HER2- subtypes: e.g. 10/209 (5%) vs. 108/669 (16%) at T1. NPV was 100% for HER2+ subtypes at T1 and T2 except for a single misclassification of a HR- tumor at T1. Only 6 tumor progressors, all HER2- were identified at T3, and all were confirmed at surgery as non-pCRs (NPV=100%). For HR+/HER2-, the NPV increased slightly from 89% at T1 to 91% at T2, while triple negative subtype had a more substantial increase, from 78% to 92%. Conclusions: Our study showed strong association between tumor progressors assessed by MRI with true non-pCRs after NAC. For HER2+ tumors, although MRI progressors are rare, they strongly indicate non-pCR at all treatment time points, while HER2- subtypes show more accurate results later in treatment. We are evaluating MRI change at 6 weeks to determine if that time point is sufficient to predict progressors. Table 1 MRI assessed tumor progression at different treatment time pointN/non-pCRs/%non-pCRMRI assessed tumor progressionT1 (after 3 weeks)T2 (inter-regimen)T3 (post-NAC)NNPV (%)NNPV (%)NNPV (%)Full cohort878/572/65%11883.14192.76100%HR+/HER2-344/280/81%4588.91190.93100%HR+/HER2+134/85/63%610021000N/AHR-/HER2+75/23/31%47521000N/Atriple negative325/184/57%6377.82692.33100% Citation Format: Wen Li, Natsuko Onishi, David C Newitt, Jessica Gibbs, Lisa J Wilmes, Ella F Jones, Bonnie N Joe, Laura S Sit, Christina Yau, A. Jo Chien, Elissa Price, Kathy S Albain, Theresa Kuritza, Kevin Morley, Judy C Boughey, Kathy Brandt, Sadia Choudhery, Amy S Clark, Mark Rosen, Elizabeth S McDonald, Anthony D Elias, Dulcy Wolverton, Kelly Fountain, David M Euhus, Heather S Han, Bethany Niell, Jennifer Drukteinis, Julie E Lang, Janice Lu, Jane L Meisel, Zaha Mitri, Rita Nanda, Donald W Northfelt, Tara Sanft, Erica Stringer-Reasor, Rebecca K Viscusi, Anne M Wallace, Douglas Yee, Rachel Yung, Smita M Asare, Michelle E Melisko, Jane Perlmutter, Hope S Rugo, Richard Schwab, W. Fraser Symmans, Laura J van't Veer, Donald A Berry, Angela DeMichele, Hiroyuki Abe, Deepa Sheth, Kirsten K Edmiston, Erin D Ellis, Richard Ha, Ralph Wynn, Erin P Crane, Charlotte Dillis, Michael Nelson, An Church, Claudine Isaacs, Qamar J Khan, Karen Y Oh, Neda Jafarian, Dae Hee Bang, Christiane Mullins, Stefanie Woodard, Kathryn W Zamora, Haydee Ojeda-Fornier, Pulin Sheth, Linda Hovanessian-Larsen, Mohammad Eghtedari, Michael Spektor, Marina Giurescu, Mary S Newell, Michael A Cohen, Elise Berman, Constance Lehman, William Smith, Kim Fitzpatrick, Marisa H Borders, Wei Yang, Basak Dogan, Sally Goudreau, Thelma Brown, Laura J Esserman, Nola M Hylton. Breast cancer subtype specific association of pCR with MRI assessed tumor volume progression during NAC in the I-SPY 2 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD9-04.

Background: Strong background parenchymal enhancement (BPE) may cause overestimation in tumor volume measured from dynamic contrast-enhanced (DCE) MRI, which may adversely affect the ability of MR tumor volume to predict treatment outcome for patients undergoing neoadjuvant chemotherapy (NAC). Specifically, an overestimation of tumor volume can result in misclassification of patients with complete pathologic response (pCR) as non-responders, leading to less confidence in MRI prediction. As well, overestimation of extent of disease might lead to more aggressive surgical therapy than necessary. This study investigated whether high BPE in the contralateral breast influences the predictive performance of MRI-measured functional tumor volume (FTV) for patients with locally advanced breast cancer undergoing NAC. Methods: patients (n=990) enrolled in the I-SPY 2 TRIAL who were randomized to the graduated experimental drug arms or controls from 2010 to 2016 were analyzed. Each patient had 4 MRI exams: pre-NAC (T0), after 3 weeks of NAC (T1), between NAC regimens (T2), and post-NAC (T3). FTV was calculated at each MRI exam by summing voxels meeting enhancement thresholds. Background parenchymal enhancement (BPE) in the contralateral breast was calculated automatically as mean percentage enhancement on the early (nominal 150sec post-contrast) image in the fibroglandular tissue segmented from 5 continuous axial slices centered in the inferior-to-superior stack. For each treatment time point, patients having both FTV and BPE measurements were included in the analysis. The area under the ROC curve (AUC) was estimated as the association between FTV and pCR at T1, T2, and T3. The analysis was conducted in the full patient cohort and in sub-cohorts defined by hormone receptor (HR) and HER2 status. In each patient cohort, a cut-off BPE value was selected to classify patients with high vs. low BPE by testing AUCs estimated with low-BPE patients reached maximum when the cut-off value varied from median to maximum in steps of 10%. Results: Out of 990 patients, 878 had pCR outcome data (pCR or non-pCR, pCR rate = 35%). Table 1 shows the number of patients, pCR rate, and AUC of FTV for predicting pCR using all patients available vs. a subset patients with low BPE (< BPE cut-off). In the full cohort, AUC increased slightly across all time points after patients with high BPE were removed. In the HR+/HER2- subtype, AUC increased at T1 after removal of cases with high BPE (0.65 vs. 0.71). For HR-/HER2+, AUC increased substantially after removal of high BPE cases (0.65 to 0.86 at T1, 0.71 to 0.87 at T2, and 0.71 to 0.89 at T3), with greater improvement at the early time point (T1) compared to later time points (T2 and T3). Only a slight improvement in the AUC was observed in the HR+/HER2+ and HR-/HER2- subtypes across all time points. Conclusions: High background parenchymal enhancement adversely affected the predictive performance of functional tumor volume measured by DCE-MRI, at early treatment time point for HR+/HER2- and across all time points for HR-/HER2+ cancer subtype. The adverse effect might be offset using subtype-optimized enhancement threshold in calculating functional tumor volume. Table 1 Effect of BPE on the prediction of pCR using FTV at various treatment time pointsT1T2T3npCR rateAUCBPE cut-offnpCR rateAUCBPE cut-offnpCR rateAUCBPE cut-offFullAll64734%0.662762334%0.701761134%0.6925Subset45334%0.6831133%0.7230534%0.72HR+/HER2-All26218%0.651924918%0.718225518%0.7519Subset13118%0.7124818%0.7120419%0.76HR+/HER2+All10636%0.642110538%0.62269634%0.7120Subset5332%0.668438%0.665740%0.73HR-/HER2+All5175%0.65204774%0.71204973%0.7116Subset3073%0.862871%0.872475%0.89HR-/HER2-All22842%0.682822243%0.751821143%0.6916Subset15940%0.7111137%0.7810540%0.75 Citation Format: Wen Li, Natsuko Onishi, David C Newitt, Roy Harnish, Ella F Jones, Lisa J Wilmes, Jessica Gibbs, Elissa Price, Bonnie N Joe, A. Jo Chien, Donald A Berry, Judy C Boughey, Kathy S Albain, Amy S Clark, Kirsten K Edmiston, Anthony D Elias, Erin D Ellis, David M Euhus, Heather S Han, Claudine Isaacs, Qamar J Khan, Julie E Lang, Janice Lu, Jane L Meisel, Zaha Mitri, Rita Nanda, Donald W Northfelt, Tara Sanft, Erica Stringer-Reasor, Rebecca K Viscusi, Anne M Wallace, Douglas Yee, Rachel Yung, Michelle E Melisko, Jane Perlmutter, Hope S Rugo, Richard Schwab, W. Fraser Symmans, Laura J van't Veer, Christina Yau, Smita M Asare, Angela DeMichele, Sally Goudreau, Hiroyuki Abe, Deepa Sheth, Dulcy Wolverton, Kelly Fountain, Richard Ha, Ralph Wynn, Erin P Crane, Charlotte Dillis, Theresa Kuritza, Kevin Morley, Michael Nelson, An Church, Bethany Niell, Jennifer Drukteinis, Karen Y Oh, Neda Jafarian, Kathy Brandt, Sadia Choudhery, Dae Hee Bang, Christiane Mullins, Stefanie Woodard, Kathryn W Zamora, Haydee Ojeda-Fornier, Mohammad Eghedari, Pulin Sheth, Linda Hovanessian-Larsen, Mark Rosen, Elizabeth S McDonald, Michael Spektor, Marina Giurescu, Mary S Newell, Michael A Cohen, Elise Berman, Constance Lehman, William Smith, Kim Fitzpatrick, Marisa H Borders, Wei Yang, Basak Dogan, Laura J Esserman, Nola M Hylton. The effect of background parenchymal enhancement on the predictive performance of functional tumor volume measured in MRI [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-02-01.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.

The purpose of this study is to evaluate the utility of MRI as a problem-solving tool for equivocal findings on diagnostic digital mammography (DM) and digital breast tomosynthesis (DBT).Breast MRI examinations performed from March 2011 to November 2014 were retrospectively reviewed to identify those examinations that were performed to further assess equivocal findings on combined DM and DBT (DM/DBT) examinations. All patients underwent diagnostic ultrasound in conjunction with their DM/DBT examination. Imaging reports were retrospectively reviewed for BI-RADS findings and assessments of diagnostic DM/DBT and diagnostic MRI examinations. A review of the electronic medical records provided information on demographic data, cancer diagnoses, and pathologic findings. Differences in the positive predictive values and negative predictive values of DM/DBT and MRI were compared using a generalized estimating equation for correlated binary data.Of 5330 MRI examinations performed during the study, 67 (1%) were performed for evaluation of an equivocal finding, including 27 asymmetries (40%), 16 focal asymmetries (24%), five masses (7%), and 19 architectural distortion (28%). MRI correlates were identified in 22 of 67 examinations (33%). Biopsies yielded a cancer diagnosis for five of 67 patients (7%). For MRI, the positive predictive value and negative predictive value were 19% and 98%, respectively, whereas for DM/DBT they were 6% and 90%, respectively (p = 0.009 and p = 0.059, respectively). The frequency of recommendations for breast MRI to evaluate equivocal findings decreased exponentially in the 3 years after DBT implementation.As clinical implementation of DBT becomes increasingly widespread, breast radiologists need an algorithm for addressing the small number of inconclusive findings that remain equivocal despite thorough DM/DBT and ultrasound examinations. Breast MRI is a useful adjunctive tool for these selected cases.

Although the majority of male breast problems are benign with gynecomastia as the most common etiology, men with breast symptoms and their referring providers are typically concerned about whether or not it is due to breast cancer. If the differentiation between benign disease and breast cancer cannot be made on the basis of clinical findings, or if the clinical presentation is suspicious, imaging is indicated. The panel recommends the following approach to breast imaging in symptomatic men. In men with clinical findings consistent with gynecomastia or pseudogynecomastia, no imaging is routinely recommended. If an indeterminate breast mass is identified, the initial recommended imaging study is ultrasound in men younger than age 25, and mammography or digital breast tomosynthesis in men age 25 and older. If physical examination is suspicious for a male breast cancer, mammography or digital breast tomosynthesis is recommended irrespective of patient age. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.