Biopsy-proven Ductal Carcinoma In Situ Research Articles

Presurgical Upgrade Prediction of DCIS to Invasive Ductal Carcinoma Using Time-dependent Deep Learning Models with DCE MRI.

Purpose To determine whether time-dependent deep learning models can outperform single time point models in predicting preoperative upgrade of ductal carcinoma in situ (DCIS) to invasive malignancy at dynamic contrast-enhanced (DCE) breast MRI without a lesion segmentation prerequisite. Materials and Methods In this exploratory study, 154 cases of biopsy-proven DCIS (25 upgraded at surgery and 129 not upgraded) were selected consecutively from a retrospective cohort of preoperative DCE MRI in women with a mean age of 59 years at time of diagnosis from 2012 to 2022. Binary classification was implemented with convolutional neural network (CNN)-long short-term memory (LSTM) architectures benchmarked against traditional CNNs without manual segmentation of the lesions. Combinatorial performance analysis of ResNet50 versus VGG16-based models was performed with each contrast phase. Binary classification area under the receiver operating characteristic curve (AUC) was reported. Results VGG16-based models consistently provided better holdout test AUCs than did ResNet50 in CNN and CNN-LSTM studies (multiphase test AUC, 0.67 vs 0.59, respectively, for CNN models [P = .04] and 0.73 vs 0.62 for CNN-LSTM models [P = .008]). The time-dependent model (CNN-LSTM) provided a better multiphase test AUC over single time point (CNN) models (0.73 vs 0.67; P = .04). Conclusion Compared with single time point architectures, sequential deep learning algorithms using preoperative DCE MRI improved prediction of DCIS lesions upgraded to invasive malignancy without the need for lesion segmentation. Keywords: MRI, Dynamic Contrast-enhanced, Breast, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024.

Adding contrast-enhanced ultrasound can improve the predictive ability of breast conventional ultrasound and mammography for pathological upgrade of biopsy-confirmed ductal carcinoma in situ

ObjectivesTo evaluate the added value of contrast-enhanced ultrasound (CEUS) on top of breast conventional imaging for predicting the upgrading of ductal carcinoma in situ (DCIS) to invasive cancer after surgery. MethodsThis retrospective study enrolled 140 biopsy-proven DCIS lesions in 138 patients and divided them into two groups based on postoperative histopathology: non-upgrade and upgrade groups. Conventional ultrasound (US), mammography (MMG), CEUS and clinicopathological (CL) features were reviewed and compared between the two groups. The predictive performance of different models (with and without CEUS features) for histologic upgrade were compared to calculate the added value of CEUS. ResultsFifty-nine (42.1 %) lesions were histologically upgraded to invasive cancer after surgery. By logistic regression analyses, we found that high-grade DCIS at biopsy (P=0.004), ultrasonographic lesion size > 20 mm (P=0.007), mass-like lesion on US (P=0.030), the presence of suspicious calcification on MMG (P=0.014), the presence of perfusion defect (P=0.005) and the area under TIC>1021.34 ml (P<0.001) on CEUS were six independent factors predicting concomitant invasive components after surgery. The CL+US+MMG model made with the four predictors in the clinicopathologic, US and MMG categories yielded an area under the receiver operating curve (AUROC) value of 0.759 (95 % CI: 0.680–0.828) in predicting histological upgrade. The combination model built by adding the two CEUS predictors to the CL+US+MMG model showed higher predictive efficacy than the CL+US+MMG model (P=0.018), as the AUROC value was improved to 0.861 (95 % CI: 0.793–0.914). ConclusionsThe addition of contrast-enhanced ultrasound to breast conventional imaging could improve the preoperative prediction of an upgrade to invasive cancer from CNB −proven DCIS lesions.

Abstract PO2-28-07: Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ

Abstract Background: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer confined within the basement membrane. Due to the increase in breast cancer screening, DCIS is increasingly being diagnosed on biopsy. Active surveillance is a novel and evolving treatment strategy for DCIS to reduce overtreatment. Currently ongoing clinical trials of active surveillance include only mammographic findings in their eligibility criteria, however mammography has limited ability to detect occult invasive cancer. The objective of this study was to investigate whether an artificial intelligence-based computer-aided diagnosis (AI-CAD) application for mammography can improve the prediction of occult invasive cancer in women with percutaneous needle biopsy-proven DCIS. Methods: A retrospective search of our database identified consecutive women with percutaneous needle biopsy-proven DCIS who underwent surgery at Seoul National University Hospital (Seoul, Korea) between June 2019 and May 2021. Two board-certified breast radiologists reviewed preoperative mammographic findings of the primary tumor in consensus according to the Breast Imaging Reporting and Data System. Using a commercially available AI-CAD (Lunit INSIGHT for Mammography, Lunit Inc.), quantitative abnormality scores of 0 to 100% of the ipsilateral breast were obtained. Data were collected on age at diagnosis, symptoms, biopsy methods, DCIS grade on biopsy, and presence or absence of invasive cancer and axillary lymph node metastases on surgical pathology. Multivariable logistic regression models were used to evaluate factors associated with prediction of occult invasive cancer. Results: Of 692 biopsy-proven DCIS in 692 women (mean age, 53 years ± 11 [standard deviation]), 298 (43%) presented as calcifications only, 160 (23%) as mass or asymmetry, and 111 (16%) as masses with calcifications. The other 123 (18%) cancers were not demonstrable on mammography. Surgical pathology revealed occult invasive cancer in 278 (40%) women and 18 (3%) had axillary metastasis. Women with occult invasive cancer showed higher abnormality scores on AI-CAD than women with pure DCIS (mean, 70% vs. 51%; P &amp;lt; .001), and women with axillary metastasis had higher abnormality scores on AI-CAD than women without axillary metastasis (mean, 88% vs. 58%; P = .002). High ( &amp;gt;75%) abnormality score on AI-CAD (Odds ratio [OR], 1.8 [95% CI: 1.3, 2.6]; P &amp;lt; .001), age of 55 years or higher (OR, 1.6 [95% CI: 1.2, 2.3]; P =.005), present symptoms in the ipsilateral breast (OR, 2.7 [95% CI: 1.9, 4.0]; P &amp;lt; .001), biopsy performed with a 14-gauge automated gun (OR, 2.5 [95% CI: 1.7, 3.6]; P &amp;lt; .001), and high-grade DCIS at biopsy (OR, 2.5 [95% CI: 1.7, 3.5]; P &amp;lt; .001] were independent predictors of occult invasive cancer with a C-index of 0.75 (95% CI: 0.72, 0.78). Conclusion: The quantitative score of preoperative mammography obtained from a commercially available AI-CAD was able to predict occult invasive cancer in an easy and simple manner. AI-CAD applications for preoperative mammography may be useful in predicting occult invasive cancer in women with biopsy-proven DCIS, especially in those without preoperative breast MRI. Citation Format: Su Hyun Lee, Hajung Kim, Su Min Ha, Soo-Yeon Kim, Jung Min Chang, Nariya Cho, Woo Kyung Moon. Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-07.

Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?

Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis. To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC). Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome. Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10-3 mm2/s (P = 0.004). Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.

A clinical radiomics nomogram preoperatively to predict ductal carcinoma in situ with microinvasion in women with biopsy-confirmed ductal carcinoma in situ: a preliminary study

PurposeTo predict ductal carcinoma in situ with microinvasion (DCISMI) based on clinicopathologic, conventional breast magnetic resonance imaging (MRI), and dynamic contrast enhanced MRI (DCE-MRI) radiomics signatures in women with biopsy-confirmed ductal carcinoma in situ (DCIS).MethodsEighty-six women with eighty-seven biopsy-proven DCIS who underwent preoperative MRI and underwent surgery were retrospectively identified. Clinicopathologic, conventional MRI, DCE-MRI radiomics, combine (based on conventional MRI and DCE-MRI radiomics), traditional (based on clinicopathologic and conventional MRI) and mixed (based on clinicopathologic, conventional MRI and DCE-MRI radiomics) models were constructed by logistic regression (LR) with a 3-fold cross-validation, all evaluated using receiver operating characteristic (ROC) curve analysis. A clinical radiomics nomogram was then built by incorporating the Radiomics score, significant clinicopathologic and conventional MRI features of mixed model.ResultsThe area under the curves (AUCs) of clinicopathologic, conventional MRI, DCE-MRI radiomics, traditional, combine, and mixed model were 0.76 (95% confidence interval [CI] 0.59–0.94), 0.77 (95%CI 0.59–0.95), 0.74 (95%CI 0.55–0.93), 0.87 (95%CI 0.73–1), 0.8 (95%CI 0.63–0.96), and 0.93 (95%CI 0.84–1) in the validation cohort, respectively. The clinical radiomics nomogram based on mixed model showed higher AUCs than both clinicopathologic and DCE-MRI radiomics models in training/test (all P < 0.05) set and showed the greatest overall net benefit for upstaging according to decision curve analysis (DCA).ConclusionA nomogram constructed by combining clinicopathologic, conventional MRI features and DCE-MRI radiomics signatures may be useful in predicting DCISMI from DICS preoperatively.

Validation and Clinical Utility of a Prediction Model for the Risk of Upstaging to Invasive Breast Cancer After a Biopsy Diagnosis Ductal Carcinoma In Situ

BackgroundThis study aimed to validate the DCIS-upstage model, a previously developed model to predict the risk of upstaging to invasive breast cancer in patients with biopsy-proven ductal carcinoma in situ (DCIS) in a more recent cohort and to assess the model’s clinical utility.MethodsThe model was validated in a registry cohort (n = 2269) and in an institution cohort (n = 302). A calibration plot was made, followed by a decision curve analysis (DCA). The model’s area under the curve (AUC) was compared with the AUC of another published model and with the AUCs of new models using the risk factors of the DCIS-upstage model and additional risk factors.ResultsThe DCIS-upstage model had an AUC of 0.67 at development; in the validation, the AUC was 0.65 in the registry cohort and 0.73 in the institution cohort. The DCA showed that the model has clinical utility. The other published model had an AUC of 0.66 in the institution cohort. Adding risk factors to the DCIS-upstage model slightly increased the AUC.ConclusionsThe DCIS-upstage prediction model is valid in other cohorts. The model has clinical utility and may be used to select patients with biopsy-proven DCIS for sentinel lymph node biopsy.

Association of quantitative MRI features of DCIS with surgical upstaging and recurrence after treatment.

e12540 Background: Ductal carcinoma in situ (DCIS) is a common preinvasive breast cancer typically identified on screening mammography. Pure DCIS is nonlethal, but 20-25% of DCIS cases identified on core biopsy upstage to invasive cancer at surgery and about half progress to invasive disease if not treated. As a result, most DCIS patients undergo excision and radiation therapy. DCIS score is a multigene assay that can aid in radiation treatment decision-making and serve as a surrogate marker of ipsilateral breast recurrence (IBR) risk. Breast MRI can accurately depict DCIS span and has potential to assess biology and IBR risk. We sought to assess the associations of advanced quantitative MRI features with upstaging and DCIS score. Methods: In this IRB-approved single institution prospective clinical trial, patients recommended for biopsy of calcifications or those who had residual calcifications after a biopsy yielding pure DCIS consented to receive a multiparametric breast MRI (dynamic contrast-enhanced and diffusion-weighted) prior to surgery. The following quantitative MRI features were obtained: functional tumor volume (FTV), volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), background parenchymal enhancement (BPE), and apparent diffusion coefficient (ADC). Patients with biopsy-proven DCIS were followed through completion of surgery to determine upstaging. DCIS score was performed in those with sufficient excision-proven pure DCIS. Associations of MRI features with invasive upstaging and DCIS score and were evaluated by Spearman’s correlation and the Wilcoxon rank-sum test. Results: Of the 120 patients enrolled in the study, 57 (48%) were diagnosed with pure DCIS on core biopsy. Fifty-five patients underwent surgery, 13 of whom (24%) upstaged to invasive disease. Thirty-eight pure DCIS lesions had sufficient tissue to generate a DCIS Score. Several MRI features were associated with upstaging and DCIS Score: Ktrans (p &lt; 0.01) was significantly higher in lesions that upstaged to invasive disease. Higher DCIS scores were associated with lower Ktrans (p = 0.04) and ve (p = 0.05) values. No statistically significant associations were observed between FTV, BPE, or ADC and invasive upstaging or DCIS Score. Conclusions: This trial suggests advanced quantitative MRI features may help identify DCIS lesions at risk for upstaging to invasive disease and IBR. Specifically, an imaging feature of vascular permeability (Ktrans) showed an expected positive association with upstaging. Imaging features of vascular permeability (Ktrans and ve) showed counterintuitive inverse associations with DCIS Scores. Future research in larger cohorts is needed to validate these findings, better determine the biological reasons for these associations, and determine whether MRI features can be used clinically to optimize DCIS treatment. Clinical trial information: NCT03495011 .

Predicting Upgrade of Ductal Carcinoma In Situ to Invasive Breast Cancer at Surgery With Ultrafast Imaging.

BACKGROUND. Biopsy-proven ductal carcinoma in situ (DCIS) lesions are often upgraded to invasive cancer at surgery. Therefore, accurate prediction of the likelihood of invasion is helpful for surgical planning, including the need for sentinel lymph node biopsy (SLNB). OBJECTIVE. The purpose of the present study was to investigate whether kinetic features of clinically available ultrafast MRI (UF-MRI) can predict upgrade of biopsy-proven DCIS to invasive cancer at surgical excision. METHODS. Consecutive patients with biopsy-proven pure DCIS lesions who underwent UF-MRI with conventional dynamic contrast-enhanced MRI (DCE-MRI) and subsequently underwent surgery between August 2019 and January 2021 were identified. Patient and lesion characteristics, biopsy method and pathology, and lesion features on mammography, ultrasound, DCE-MRI, and UF-MRI were assessed to determine predictors of upgrade to invasive cancer. The Fisher exact test and Kruskal-Wallis test were used for association analysis. RESULTS. In 68 patients (median age, 52.0 years; range, 31-79 years) with 68 biopsy-proven pure DCIS lesions, 26 lesions (38%) were upgraded from in situ to invasive cancer. An upgrade of DCIS to invasive cancer was significantly associated with a shorter time to enhancement (TTE) on preoperative UF-MRI (p = .03), with a threshold of 11 seconds providing maximum specificity (50%) and sensitivity (76%) for upgrade. Larger lesion size on DCE-MRI (p = .001) and mammography (p = .04) was also significantly associated with upgrade; an optimal predictive threshold of 4.4 cm on DCE-MRI yielded sensitivity of 88% and specificity of 56%. No other specific variables were significantly associated with upgrade after surgery. Logistic regression of selected features combined with TTE produced a higher AUC (0.85) in predicting upgrade to invasive disease than did each factor alone, but this result was not statistically significant. CONCLUSION. Preoperative UF-MRI TTE and lesion size on DCE-MRI and mammography show potential in predicting upgrade of DCIS to invasive cancer at surgery. CLINICAL IMPACT. UF-MRI provides useful information that can be used in surgical planning, including determination of the need to perform SLNB.

Predicting Lymph Node Metastases in Patients with Biopsy-Proven Ductal Carcinoma In Situ of the Breast: Development and Validation of the DCIS-met Model

PurposeIn patients with a biopsy-proven ductal carcinoma in situ (DCIS), axillary staging is frequently performed, but in hindsight often turns out to be superfluous. The aim of this observational study was to develop a prediction model for risk of lymph node metastasis in patients with a biopsy-proven DCIS.MethodsData were received from the Dutch Pathology Databank and the Netherlands Cancer Registry. The population-based cohort consisted of all biopsy-proven DCIS patients diagnosed in the Netherlands in 2011 and 2012. The prediction model was evaluated with the area under the curve (AUC) of the receiver operating characteristic, and a calibration plot and a decision curve analysis and was validated in a Dutch cohort of patients diagnosed in the period 2016–2019.ResultsOf 2892 biopsy-proven DCIS patients, 127 had metastasis (4.4%). Risk factors were younger age (OR = 0.97, 95% CI 0.95–0.99), DCIS not detected by screening (OR = 1.55, 95% CI 1.01–2.38), suspected invasive component at biopsy (OR = 1.86, 95% CI 1.01–3.41), palpable tumour (OR = 2.06, 95% CI 1.34–3.18), BI-RADS score 5 (OR = 2.41, 95% CI 1.53–3.78), intermediate-grade DCIS (OR = 3.01, 95% CI 1.27–7.15) and high-grade DCIS (OR = 3.20, 95% CI 1.36–7.54). For 24% (n = 708) of the patients, the predicted risk of lymph node metastasis was above 5%. Based on the decision curve analysis, the model had a net benefit for a predicted risk below 25%. The AUC was 0.745. Of the 2269 patients in the validation cohort, 53 (2.2%) had metastasis and the AUC was 0.741.ConclusionsThis DCIS-met model can support clinical decisions on axillary staging in patients with biopsy-proven DCIS.

Abstract B021: Use of wide field optical coherence tomography (WF-OCT) in margin assessment during breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS)

Abstract Purpose: To assess the utility of a novel imaging technology for intraoperative margin assessment in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Background: The multi-focal nature of DCIS presents a challenge to ensuring negative margins during BCS. Routine methods for intraoperative margin assessment, such as specimen radiography, ultrasound, cavity margins, and touch prep cytology each have specific limitations, including operator skill, time delay, probe position, and specimen completeness. A more recent method, wide field optical coherence tomography (WF-OCT), enables real-time tissue visualization at up to 2 mm of depth with the ability to use image-based machine learning to identify regions of interest suspicious for residual malignancy. Methods: Two adult females with biopsy-proven DCIS and one with invasive carcinoma underwent BCS following routine surveillance mammography and were prospectively evaluated. Primary lesions were imaged intraoperatively with specimen radiography and a WF-OCT imaging device (OTIS, Perimeter Medical AI, Toronto, Canada); images from both modalities were read to identify potential residual malignancy, and additional tissue was excised as indicated. Permanent histopathology was compared to imaging results. Results: The first patient (76 y/o, BI-RADS 4B, 1.6 cm) underwent BCS and the excised sample was 4 x 3.7 x 3.2 cm. By radiography, the biopsy clip and localization reflector were within the specimen and margins appeared satisfactory; WF-OCT demonstrated residual disease at the inferior margin and additional tissue was excised. Permanent histology showed DCIS involvement of inferior primary margin; additional margin excision contained DCIS and was negative. The second patient (64 y/o, BI-RADS 4B, 1 cm) underwent BCS and the excised sample was 4 x 3.5 x 3.5. By radiography, the biopsy clip and reflector were within the specimen and margins appeared satisfactory; WF-OCT showed residual disease at the inferior and posterior margins and additional tissue was excised. Permanent histology demonstrated DCIS within 1 mm and pleomorphic lobular carcinoma in situ (LCIS) microns from primary inferior margin; the additional inferior sample was margin negative, and posterior sample contained pleomorphic LCIS and was margin negative. The last patient (76 y/o, BI-RADS 5, 1.9 x 1.9 x 1.7 cm) underwent BCS and the excised sample was 6.5 x 5.3 x 4.2 cm. By radiography, the biopsy clip and localization reflector were within the specimen and margins appeared satisfactory; WF-OCT showed residual disease at the lateral margin and also revealed occult DCIS not found on biopsy. Additional tissue was taken until margin clearance by WF-OCT. Permanent histology demonstrated DCIS to &amp;lt;1 mm of primary lateral margin; the additional excision contained DCIS and was margin negative. Conclusions: In this case series of 3 adult females undergoing BCS for breast carcinoma, WF-OCT was a beneficial adjunctive imaging modality to specimen radiography for margin assessment. Citation Format: Amelia B. Tower, Andrew Berkeley. Use of wide field optical coherence tomography (WF-OCT) in margin assessment during breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) [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 B021.

Ductal Carcinoma In Situ (DCIS) Diagnosed by MRI-Guided Biopsy among BRCA1/BRCA2 Mutation Carriers.

While BRCA1/BRCA2 pathogenic sequence variants (PSVs) clearly confer an increased risk for invasive breast cancer, the extent to which these mutant alleles increase DCIS risk is less clear. To assess the rate of detection over a 5-year period, and MRI imaging features of pure noncalcified DCIS in a cohort of Israeli BRCA1/BRCA2 PSV carriers attending a high-risk clinic from 2015 to 2020. All female BRCA1/BRCA2 PSV-carriers followed at the Meirav High-risk clinic from 2015 to 2020 were eligible if they underwent semiannual breast imaging (MRI/mammography) and MRI-guided biopsy-proven pure DCIS. Clinical data, pathology information, and imaging characteristics were retrieved from the computerized archiving system. 18/121 (15.2%) participating BRCA1 PSV carriers and 8/81 (10.1%) BRCA2 PSV-carriers who underwent MRI-guided biopsy were diagnosed with DCIS. The median age of BRCA1 carriers and BRCA2 carriers was 49.8 years and 60.6 years, respectively (p = 0.55). Negative estrogen-receptor tumors were diagnosed in 13/18 (72%) BRCA1 and 2/8 (25%) BRCA2 PSV carriers (p < 0.05). Thirteen (13/18-72%) BRCA1 carriers had intermediate to high-grade or high-grade DCIS compared with 4/8 (50%) of BRCA2 carriers (p = 0.03). Over the 5-year study period, 29/1100 (2.6%) BRCA1/BRCA2 PSV carriers were diagnosed with DCIS seen on MRI only. MRI-detected noncalcified DCIS is more frequent in BRCA1 PSV carriers compared with BRCA2 carriers, unlike the BRCA2 predominance in mammography-detected calcified DCIS. BRCA1-related DCIS is diagnosed earlier, more likely to be estrogen receptor-negative and of higher grade compared with BRCA2-related DCIS. Future prospective studies should validate these results and assess the actual impact they might have on clinical management of BRCA PSV carriers.

Diffusion-weighted Breast MRI in Prediction of Upstaging in Women with Biopsy-proven Ductal Carcinoma in Situ.

Background Accurate preoperative prediction of upstaging in women with biopsy-proven ductal carcinoma in situ (DCIS) is important for surgical planning, but published models using predictive MRI features remain lacking. Purpose To develop and validate a predictive model based on preoperative breast MRI to predict upstaging in women with biopsy-proven DCIS and to select high-risk women who may benefit from sentinel lymph node biopsy at initial surgery. Materials and methods Consecutive women with biopsy-proven DCIS who underwent preoperative 3.0-T breast MRI including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) and who underwent surgery between June 2019 and March 2020 were retrospectively identified (development set) from an academic medical center. The apparent diffusion coefficients of lesions from DWI, lesion size and morphologic features on DCE MRI scans, mammographic findings, age, symptoms, biopsy method, and DCIS grade at biopsy were collected. The presence of invasive cancer and axillary metastases was determined with surgical pathology. A predictive model for upstaging was developed by using multivariable logistic regression and validated in a subsequent prospective internal validation set recruited between July 2020 and April 2021. Results Fifty-seven (41%) of 140 women (mean age, 53 years ± 11 [SD]) in the development set and 43 (41%) of 105 women (mean age, 53 years ± 10) in the validation set were upstaged after surgery. The predictive model combining DWI and clinical-pathologic factors showed the areas under the receiver operating characteristic curve at 0.87 (95% CI: 0.80, 0.92) in the development set and 0.76 (95% CI: 0.67, 0.84) in the validation set. The predicted probability of invasive cancer showed good interobserver agreement (intraclass correlation coefficient, 0.79); the positive predictive value was 85% (28 of 33), and the negative predictive value was 92% (22 of 24). Conclusion A predictive model based on diffusion-weighted breast MRI identified women at high risk of upstaging. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Baltzer in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Reoperation rate of ductal carcinoma in situ: impact of tomosynthesis (3D) and spot magnification.

Surgical planning depends on precise preoperative assessment of the radiological extent of ductal carcinoma in situ (DCIS). Despite different modalities used, reoperation rates for DCIS due to involved margins are high. To evaluate the impact of additional imaging views (spot magnification, tomosynthesis) on surgical reoperation rate of DCIS. The retrospective single institute study includes 157 patients with biopsy-proven pure DCIS seen on mammogram as microcalcifications and treated with breast-conserving surgery. Patients have been divided into three groups according to additional imaging performed: spot magnification, tomosynthesis, and none. All breast images (mammograms, spot magnification, tomosynthesis) were reviewed and the maximum extent of pathological microcalcifications was recorded. Radiological size was compared to final histopathological size. Reoperation rate due to inadequate margins was recorded. Reoperation rates (25%) due to inadequate margins were as follows: spot (18%), tomosynthesis (27%), none (31%); P = 0.488. Spot magnification, tomosynthesis, and digital zoom of full-field digital mammography predicted similarly the final histopathological size. Reoperation group had a significantly greater preoperative radiological median size (26 mm vs. 20 mm; P = 0.014) as well as median size of disease on final histopathological report (29 mm vs. 14 mm; P < 0.001). Discrepancy between radiological and final histopathological size became greater with increasing DCIS extent. The main factors for reoperations are DCIS size and discordance between radiological and histopathological sizes. The use of additional imaging views (spot magnification, tomosynthesis) did not reduce reoperation rate.

Abstract P3-19-12: Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial

Abstract Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [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 P3-19-12.

PP37 Presentation Time: 11:50 AM: Intra-Operative Radiation Therapy (IORT) Using Electronic Brachytherapy in Treatment of Early-Stage Breast Cancer Patients (pts) with Ductal Carcinoma In Situ (DCIS)

Purpose: An institutional review board (IRB)-approved single arm prospective non-randomized multi-institution trial was designed to determine the efficacy and outcome of single fraction IORT at the time of breast conserving surgery for early-stage breast cancer. A subset of this trial included women age > 40 years with biopsy-proven DCIS < 30 mm by pre-operative clinical and radiographic evaluation. Preliminary results of this DCIS pt subset were reviewed.

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast.

In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

The usefulness of ultrafast MRI evaluation for predicting histologic upgrade of ductal carcinoma in situ

PurposeThe purpose of this study was to investigate the usefulness of ultrafast MRI with conventional dynamic contrast-enhanced (DCE)-MRI for predicting histologic upgrade of ductal carcinoma in situ (DCIS) to invasive cancer. MethodsThis retrospective study enrolled 53 biopsy-proven DCIS lesions in 53 patients and divided into two groups based on postoperative histopathologic diagnoses: non-upgrade and upgrade to invasive cancer groups. Imaging features of conventional DCE-MRI and ultrafast MRI, and histopathologic features were reviewed and compared between the two groups. Interobserver agreements for MRI features were analyzed by two radiologists. The radiologic and histopathologic parameters for predicting histologic upgrade of DCIS were identified using multiple linear regression. ResultsSeventeen lesions (32.1 %) were histologically upgraded to invasive cancer after surgery. The interobserver agreement for ultrafast MRI parameters was excellent, and maximum slope (MS) and maximum enhancement (ME) showed the highest reliability (intraclass correlation coefficients, 0.907 and 0.897, respectively). The upgrade group showed significantly larger lesion size on MRI (median 40 mm [25th to 75th percentiles 16.0–83.0] vs. 18.5 mm [10.0−29.8], p < 0.001), higher MS (12.1 %/s [8.2−13.9] vs. 8.7 %/s [6.4−11.1], p = 0.004), and higher ME (236.5 % [153.7−253.7] vs. 175.4 % [140.1−207.7], p = 0.027) than non-upgrade group. Lesion size (≥ 20 mm), MS (> 11.5 %), and ME (> 229.1 %) were significant predictors for histologic upgrade, which could predict 10 cases of histologic upgrade (10/17, 58.8 %) without a false-positive case. ConclusionPreoperative ultrafast MRI with conventional DCE-MRI could be useful in management decisions for DCIS patients.

Preoperative breast MRI in management of patients with needle biopsy-proven ductal carcinoma in situ (DCIS)

BackgroundIn 20–25% of patients with biopsy-proven DCIS underestimation occurs. Sentinel lymph node biopsy (SLNB) is offered to patients with biopsy-proven ductal carcinoma in situ (DCIS) and a high risk of occult invasive cancer. However, assessment of high risk is controversial. We aimed to improve selection of patients for SLNB with preoperative breast magnetic resonance imaging (MRI). MethodsIn this prospective observational study, MRI was offered to all subsequent patients with a biopsy-proven DCIS admitted to a large Dutch teaching hospital between April 2012 and March 2017. MRI images were analysed for signs of invasive cancer and the results were compared with the pathologic results after surgical treatment. The diagnostic accuracy of additional MRI in detecting occult invasive cancer was determined. ResultsOf 211 patients eligible for additional MRI analysis, 149 underwent breast MRI. The majority (67%) received breast-conserving therapy, and the underestimation rate was 20%. Subsequent to MRI analysis, 20 additional invasive diagnostic procedures were performed. Occult invasive cancer was suspected on MRI in 46 patients (31%) and was confirmed in 18 (12%). In this study, breast MRI had a sensitivity of 67%, a specificity of 77%, and a true negative rate of 91%. ConclusionPreoperative breast MRI cannot reliably predict the presence of invasive cancer in patients with biopsy proven DCIS. Therefore, it cannot be used to in the selection of patients for a SLNB.

Abstract P6-16-06: Improved early stratification of invasive cancer risk using MRI in a ductal carcinoma in-situ short-term active surveillance cohort treated with neoadjuvant endocrine therapy

Abstract Purpose Standard treatment for ductal carcinoma in situ (DCIS) involves surgical excision and radiation treatment, and often adjuvant endocrine therapy (ET). However, this may constitute overtreatment for some women. The purpose of this neoadjuvant ET study in patients with biopsy-proven DCIS was to evaluate the relationship between the primary outcome of upstaging at surgery (invasive disease) and changes in the pre- and post-ET MRI appearances of both (1) lesion and (2) background parenchymal enhancement (BPE), with the goal to better inform de-escalated therapy. Methods Outcomes of patients with DCIS who were prospectively enrolled in a neoadjuvant ET trial between 2002 and 2009 were retrospectively analyzed with IRB approval. All patients had dynamic contrast-enhanced breast MRI prior to and following an average of 3.1 months of ET (range 1.9 – 5 months), followed by surgical excision within one year of the second MRI. Pathology reports were used to confirm initial biopsy results and to determine the nature and extent of disease postoperatively. Surgeon and radiologist’s reports were used to assess improvement of lesion after ET based on 1) less prominently enhancing pattern or 2) reduction in size of DCIS lesion after treatment. BPE response to ET on imaging was assessed by two radiologists specialized in breast imaging who compared pre- and post-ET MRI’s, blinded to all imaging reports. The change in BPE of the ipsilateral breast with treatment was scored subjectively as increased, decreased, or unchanged. Readers reached a consensus on discordant classifications of the change in BPE. The correlation between imaging change (of lesion and BPE) and incidence of invasive ductal carcinoma (IDC) at surgery was determined using Fisher’s exact test. Results: Of 34 patients evaluated, six (18%) had IDC at surgery. The prevalence of IDC in each group is shown in Table 2. Those with improvement of lesion on MRI had a lower likelihood of IDC at surgery compared to patients with no imaging improvement (Table 2, p= 0.048). Addition of change in BPE to the evaluation of lesion improvement significantly increased the chance of identifying specific patients who were much more likely to have an underlying invasive cancer at surgery (Table 2, p= 0.032). The risk of having IDC at surgery was considerably higher in the group whose lesion was assessed as not improved and who had decreased BPE scores on MRI (Table 2, p= 0.018). Conclusion: In our unique population of patients with mostly ER+ DCIS receiving pre-operative endocrine therapy, the combination of lack of lesion improvement and reduction in BPE score in blinded reads was significantly associated with the finding of invasive disease at surgical excision. This result may reflect the unmasking of a more aggressive lesion in those with underlying IDC and help identify patients with a higher likelihood of the presence of IDC at surgery. Although this study is small, it suggests that risk-stratifying patients with DCIS based on lesion and parenchymal imaging features associated with treatment response may aid in tailoring therapy for DCIS. We are testing this prospectively in an active surveillance cohort. Table 1. Incidence of IDC at surgery depending on image features (n= 34)Improvement of lesion in MRINo Improvement of lesion in MRIP-value (Fisher’s Exact Test)&amp; No Reduction in BPE&amp; Reduction in BPE&amp; No Reduction in BPE&amp; Reduction in BPEIncidence of IDC at surgery (n)0204Incidence of Not IDC at surgery (n)121024%IDC at surgery when assessing lesion only (%)9.1%40%0.048*%IDC at surgery when assessing lesion AND BPE (%)0%16.7%0%50%0.032*%IDC at surgery when assessing lesion AND BPE (%)8.3%50%0.018* Citation Format: Paul Kim, Heather I. Greenwood, Rita I. Freimanis, Gillian L Hirst, Megan Fischer-Colbrie, Jessica Gibbs, Nola M Hylton, Christina Yau, Eun-Sil Shelley Hwang, Laura J. Esserman, Rita A Mukhtar. Improved early stratification of invasive cancer risk using MRI in a ductal carcinoma in-situ short-term active surveillance cohort treated with neoadjuvant endocrine therapy [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 P6-16-06.

Abstract P3-10-28: The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast

Abstract Purpose/Objectives: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of adding HER2-directed therapy to HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the impact of HER2 status on DCIS patient outcomes as well as the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. Materials/Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Only patients with known estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status were included in the analysis. Patients were divided into two groups based on the adjuvant therapy they received: systemic therapy (assumed to be HER2-directed targeted therapy) or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Results: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy, while 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy were likely more likely to be ER-negative. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariate analysis. Factors associated with worse OS on multivariate analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. Conclusions: In the largest study to date evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding. Citation Format: Lewis GD, Haque W, Farach A, Hatch SS, Butler EB, Schwartz MR, Bonefas E, Teh BS. The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast [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 P3-10-28.