Biopsy-proven Ductal Carcinoma Research Articles

Safety and margin positivity rates of surgeon-performed intraoperative ultrasound-guided wire localization for breast cancer

BackgroundSurgeon-performed intraoperative ultrasound-guided wire localization (IOL) offers an improved patient experience and decreased cost compared to preoperative localization by radiology, yet literature on this technique is sparse. Here we evaluate the safety and margin positivity rate after surgeon-performed IOL for breast cancer. MethodsPatients with biopsy-proven breast malignancy and planned breast conservation who underwent IOL by a single breast surgeon between 2017–2023 and had follow-up at our institution were retrospectively identified. Patient and tumor characteristics, method of diagnosis, imaging findings, use of oncoplastic surgery, and follow-up data were analyzed. ResultsA total of 137 IOLs were performed for biopsy-proven ductal carcinoma in situ (DCIS) or invasive cancer. The median patient age was 69 years. Most patients had a non-palpable tumor (n = 104, 76.5%). 84.6% of patients underwent pre-operative biopsy by ultrasound guidance, 12.5% by stereotactic guidance, and 2.9% by MRI. In total, 7.3% of patients (n = 10) had positive margins, including 2 with invasive disease at the margin and 8 with DCIS at the margin. Nine patients underwent re-excision for positive or close margins, of which 8 had successful margin-negative breast conservation and 1 patient underwent mastectomy. Thirty-day postoperative complications occurred in 21 patients (15.3%). Of these, most (n = 19, 90.4%) had minor complications including seroma (n = 14), cellulitis (n = 3), and skin allergy (n = 2). At median follow-up of 20.4 months, no patients experienced recurrence. ConclusionsIn our single-surgeon series, IOL is a safe technique for localization of invasive carcinoma and DCIS with margin positivity, re-excision, and postoperative complication rates within previously published ranges. SynopsisThis study evaluates the safety of and re-excision rates after intraoperative surgeon-performed ultrasound-guided wire localization (IOL) for breast cancer. Results demonstrate margin positivity and re-excision rates equivalent to or lower than rates reported in literature utilizing preoperative localization techniques.

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 < .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 ( >75%) abnormality score on AI-CAD (Odds ratio [OR], 1.8 [95% CI: 1.3, 2.6]; P < .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 < .001), biopsy performed with a 14-gauge automated gun (OR, 2.5 [95% CI: 1.7, 3.6]; P < .001), and high-grade DCIS at biopsy (OR, 2.5 [95% CI: 1.7, 3.5]; P < .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.

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.

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.

Artificial Intelligence for Neuroimaging and Musculoskeletal Radiology: Overview of Current Commercial Algorithms

To assess differences in the mammographic and sonographic appearance of breast cancer in African American (AA) and Non-Latina White (NLW) women.We identified AA and NLW women with biopsy proven ductal carcinoma in situ or invasive breast cancer between June 1, 2015 and May 31, 2018. Racial differences in Breast Imaging and Reporting Data System (BI-RADS) imaging features were analyzed by imaging cohorts, i.e. screen detected vs. clinical presentation, using logistic regression adjusted for histology and molecular subtypes.We analyzed 270 AA women with 278 cancers (166 screen detected, 112 clinical) and 586 NLW women with 599 cancers (397 screen detected, 202 clinical). Compared with NLW women, AA women had higher rates of non-dense breast composition (almost entirely fatty 12.0% vs. 4.6%, scattered fibroglandular 50.9% vs. 45.2%; overall P < 0001) in both cohorts and were less likely to have screen detected architectural distortion, (odds ratio (OR) = 0.38, 95% CI 0.18–0.80). AA women were less likely than NLW women to have screen detected irregular than oval/round masses (mammography: OR = 0.36, 95% CI 0.19–0.68; sonography: OR = 0.48, 95% CI 0.24–0.94), and more likely to present clinically with high density masses (OR = 3.03, 95% CI 1.12–8.20) demonstrating posterior enhancement (OR = 3.02, 95% CI 1.11–8.27).There are racial differences in the mammographic and sonographic appearance of breast cancer even after accounting for higher rates of triple negative breast cancer in AA women. Understanding these differences may provide breast imagers with a framework to approach breast cancer diagnosis in the AA population in clinical practice.

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

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

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.

A comparison of the imaging appearance of breast cancer in African American women with non-Latina white women

PurposeTo assess differences in the mammographic and sonographic appearance of breast cancer in African American (AA) and Non-Latina White (NLW) women. MethodsWe identified AA and NLW women with biopsy proven ductal carcinoma in situ or invasive breast cancer between June 1, 2015 and May 31, 2018. Racial differences in Breast Imaging and Reporting Data System (BI-RADS) imaging features were analyzed by imaging cohorts, i.e. screen detected vs. clinical presentation, using logistic regression adjusted for histology and molecular subtypes. ResultsWe analyzed 270 AA women with 278 cancers (166 screen detected, 112 clinical) and 586 NLW women with 599 cancers (397 screen detected, 202 clinical). Compared with NLW women, AA women had higher rates of non-dense breast composition (almost entirely fatty 12.0% vs. 4.6%, scattered fibroglandular 50.9% vs. 45.2%; overall P < 0001) in both cohorts and were less likely to have screen detected architectural distortion, (odds ratio (OR) = 0.38, 95% CI 0.18–0.80). AA women were less likely than NLW women to have screen detected irregular than oval/round masses (mammography: OR = 0.36, 95% CI 0.19–0.68; sonography: OR = 0.48, 95% CI 0.24–0.94), and more likely to present clinically with high density masses (OR = 3.03, 95% CI 1.12–8.20) demonstrating posterior enhancement (OR = 3.02, 95% CI 1.11–8.27). ConclusionThere are racial differences in the mammographic and sonographic appearance of breast cancer even after accounting for higher rates of triple negative breast cancer in AA women. Understanding these differences may provide breast imagers with a framework to approach breast cancer diagnosis in the AA population in clinical practice.

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.

Abstract 458: Development and validation of convolutional neural network to identify regions of interest in lumpectomy margins using optical coherence tomography

Abstract Background/Objective: Optical coherence tomography (OCT) is the optical analog of high-frequency ultrasound and produces real-time, high-resolution images up to 2 mm deep. Multi-reader studies of OCT have shown differentiation of normal parenchyma from neoplasms, including DCIS and cancers, with &amp;gt;85% sensitivity and specificity. Intraoperative evaluation of breast lumpectomy margins (LMs) with OCT may help achieve negative margins at primary surgery and avoid re-excision. Artificial Intelligence can be trained to spot regions of interest (ROI) in OCT LM images suspicious for malignancy. The purpose of this study was to develop and validate an automated convolutional neural network (CNN) to screen OCT LM images for ROIs. Methods: Following IRB approval, LMs from 126 patients with ductal malignancy were OCT imaged. Images were compared to corresponding permanent histology and annotated by breast pathologists to create a training set of 25,000 control ROIs. A CNN algorithm was developed with 3 convolutional layers, a 3x3 kernel, and 3 fully connected layers to perform binary classification of images as “suspicious” or “non-suspicious” for malignancy. A weighted loss function was used to balance the training data for non-suspicious vs. suspicious images and to tune sensitivity and specificity. Once trained and weighted, the CNN was tested in a prospective study using OCT images of 29 LMs from 29 patients with biopsy-proven ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), or both. CNN results were compared to permanent histology. Results: The patient population was 61.5 ± 7.3 years old, 100% female, with Stage 0-1 disease. Disease included IDC (n=20), invasive lobular (n=2), DCIS (n=27), mixed (n=74), atypical ductal hyperplasia (n=24), as well as benign findings including atypical lobular hyperplasia (n=19), lymphatic invasion (n=13), lobular carcinoma in situ (n=12), usual ductal hyperplasia (n=35), and duct ectasia (n=17). Following primary surgery, LMs were scanned using OCT and images were CNN analyzed. Approximately 1.9 M OCT ROIs were assessed, identifying 101,099 suspicious ROIs. Three hundred and eighty-four (384) ROIs were correctly identified, yielding a 70% true positive and 5.2% false positive rate with 70% sensitivity and 96% specificity. The receiver operating curve is shown below. Conclusions: Automated analysis of OCT images using a trained CNN to identify ROIs suspicious for DCIS or IDC in LMs is feasible, demonstrating high concordance with permanent pathology. These findings indicate the utility of AI for screening OCT images with potential utilization for intraoperative evaluation of LMs. A pivotal prospective clinical trial will be necessary to evaluate breast specimens in real time to determine if this application may improve re-excision rates in lumpectomy. Citation Format: David Rempel, Andrew Berkeley, Chandandeep Nagi, Vladimir Pekar, Margaret Burns, Beryl Augustine, Alia Nazarullah, Ismail Jatoi, Kelly K. Hunt, Alastair Thompson, Savitri Krishnamurthy. Development and validation of convolutional neural network to identify regions of interest in lumpectomy margins using optical coherence tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 458.

Development and Validation of a Prediction Model for Positive Margins in Breast-Conserving Surgery.

BackgroundThe chances of second surgery due to positive margins in patients receiving breast-conversing surgery (BCS) were about 20-40%. This study aims to develop and validate a nomogram to predict the status of breast-conserving margins.MethodsThe database identified patients with core needle biopsy-proven ductal carcinoma in situ (DCIS) or invasive breast carcinoma who underwent BCS in Shanxi Bethune Hospital between January 1, 2015 and December 31, 2021 (n = 573). The patients were divided into two models: (1) The first model consists of 398 patients who underwent BCS between 2015 and 2019; (2) The validation model consists of 175 patients who underwent BCS between 2020 and 2021. The development of the nomogram was based on the findings of multivariate logistic regression analysis. Discrimination was assessed by computing the C-index. The Hosmer-Lemeshow goodness-of-fit test was used to validate the calibration performance.ResultsThe final multivariate regression model was developed as a nomogram, including blood flow signals (OR = 2.88, p = 0.001), grade (OR = 2.46, p = 0.002), microcalcifications (OR = 2.39, p = 0.003), tumor size in ultrasound (OR = 2.12, p = 0.011) and cerbB-2 status (OR = 1.99, p = 0.042). C-indices were calculated of 0.71 (95% CI: 0.64-0.78) and 0.68 (95% CI: 0.59-0.78) for the modeling and the validation group, respectively. The calibration of the model was considered adequate in the validation group (p > 0.05).ConclusionWe developed a nomogram that enables the estimation of the preoperative risk of positive BCS margins. Our nomogram provides a valuable tool for identifying high-risk patients who might have to undergo a wider excision.

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.

Identification of Early Molecular Markers for Breast Cancer

Background: Early detection of DCIS is very important because it is a highly curable disease, with a 10-year cancer-specific survival rate of over 97%. The biomarkers and immunehistochemical markers (Osteopontin OPN) SPP1, MUC1 (Epithelial Mucin 1), RRM2 (Ribonucleotidereductase), FOXM1 (Forkhead box M1) DEPDC1 (DEP (Disheveled, EGL-10, and Pleckstrin) domain-containing protein), Nucleolar spindle-associated protein (NUSAP1), EXO1 (Exonuclease 1), are expressed strongly right from DCIS and thereby with early diagnosis of this preinvasive condition with progression to invasive carcinoma, improves the prognosis of breast cancer. Aim: To study the markers (Osteopontin OPN) SPP1, MUC1 (Epithelial Mucin 1), RRM2 (Ribonucleotidereductase), FOXM1 (Forkhead box M1) DEPDC1 (DEP (Disheveled, EGL-10, and Pleckstrin) domain-containing protein), Nucleolar spindle-associated protein (NUSAP1), EXO1 (Exonuclease 1 by immunohistochemistry for early detection and prognostication of breast Cancers. Methods: This is a prospective case control study in 50 females with mammographically suspected and FNAC and biopsy proven Ductal Carcinoma in situ (25 cases) and infiltrating ductal carcinoma (25 cases) with 50 healthy control samples. The paraffin blocks of the tissue sections were stained with hematoxylin and eosin evaluated by light microscopy and immunohistochemistry performed with DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1, SPP1 (Osteopontin). Observations: In DCIS and invasive ductal carcinoma the immunohistochemical marker expression of DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1are increased as compared to healthy controls where there is absence of any kind of staining for these IHC markers except for some exceptional case where there is weak positive staining. Conclusions: These IHC markers aid in early detection of DCIS and invasive carcinomas as these markers are not expressed in healthy control tissue. The similarities between antigen expression as evidenced by immunohistochemistry in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS progressing to invasive carcinoma by detection of biomarkers by immunohistochemistry is of utmost relevance for the survival of patients who are at high risk of developing breast carcinoma.

Electronic Brachytherapy at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer: Early Follow-Up Results of a Nonrandomized, Multicenter Trial

To describe early follow-up results of a trial of single-fraction, intra-operative radiation therapy (IORT) delivered with an electronic brachytherapy system immediately following surgical resection for treatment of early-stage breast cancer. To date, 1,028 participants have been enrolled in this open label, single-arm, prospective, non-randomized trial at 28 hospitals in the USA (27) and Portugal (1). 1,023 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by IORT to the lumpectomy cavity. A presterilized lead shield was placed on the chest wall and a balloon applicator suitable to the surgical bed was placed in the lumpectomy cavity and inflated with saline (30-75 cc). Balloon surface-to-skin distance of ≥ 1.0 cm was confirmed by ultrasound. Single-fraction IORT (20 Gy) was delivered at the balloon applicator surface with a mean radiation treatment time of 11.3 minutes. Following IORT, balloon was deflated and removed along with lead shielding, and surgical site was sutured. The prespecified primary outcome of this 10-year follow-up study is ipsilateral breast tumor recurrence at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Median follow-up time was 1.2 years with 320, 102, and 10 participants completing 2-, 3-, and 4-year follow-up, respectively. Mean age at enrollment was 66 years (range 41-93). 246 participants had DCIS and 777 had invasive ductal carcinoma. DCIS nuclear grades were high (82), intermediate (119), or low (45) with three identified as bilateral. Invasive cancers were Grade 1 (318) including two bilateral cases, Grade 2 (340) with one bilateral case, Grade 3 (105) with two bilateral cases, or no Grade (14). Mean tumor size was 12.01 ± 10.8 mm. Cosmesis was excellent in 100% of participants at 4-year follow-up and excellent to good in 94% and 91% of participants at 2- and 3-year follow-up, respectively. The number of reported adverse events (AEs) that were Grade 2 or higher was 169 (9%). Seroma, breast induration, erythema, breast fibrosis, and breast pain were the most frequent AEs. There were ten deaths, none of which were breast cancer related. There were six ipsilateral breast recurrences and three new contralateral breast cancers. Single-fraction IORT using an electronic brachytherapy system following breast conservation surgery may be a promising treatment option for select early-stage breast cancer patients. Early findings from this multicenter trial suggest that the short and convenient course of radiation therapy has low morbidity, excellent to good cosmetic results, and a low rate of high-grade adverse events and recurrences.

Abstract P1-10-19: Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.

Abstract P1-10-20: A multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer: Early results of unplanned boost participants

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered as a boost using the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. Upon the presence of additional risk factors, 37 participants subsequently received whole breast radiation therapy (WBRT); thus, these participants received an unplanned IORT boost and were removed from the primary analysis but will continue to be followed for the duration of the 10-year study. Cosmesis (Harvard Scale) was assessed in this subset of participants. The primary outcome for the main trial is recurrence of ipsilateral breast tumor at 5 years. Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Early Findings 37 boost participants received WBRT (up to 50 Gy) after IORT (36 received the prescribed 20 Gy dose; one received 14 Gy). Mean follow-up time was 430 days (range 13-1119). Mean age at IORT was 62 years (range 45-78). Boost participants had either DCIS (N=5) or invasive ductal carcinoma (N=32). The DCIS nuclear grade was high (N=3), intermediate (N=1), or low (N=1). Invasive cancers were Grade 1 (N=15), 2 (N=10), 3 (N=6), or unknown (N=1). 29 participants had T1, 3 had T2, and 5 had Tis lesions. Mean tumor size was 13.04 ± 10.26 mm. For the two participants who have reached 3-year follow-up, cosmesis was excellent (N=1) and fair (N=1). For the six participants who have reached 2-year follow-up, cosmesis was excellent (N=4), good (N=1), and fair (N=1). There was one serious adverse event with a Grade 3 for skin necrosis. The most frequent side effects were seroma (10%), edema (9%), pain (9%), erythema (6%), and induration (5%). There have been no deaths, recurrences, or new primary tumors among the boost participants to date. Conclusions Early results from this multi-center trial suggest that IORT as a tumor-bed boost using the Xoft Axxent eBx System at the time of breast conservation surgery is safe and has low morbidity. To date, the majority of participants receiving an unplanned IORT boost have had excellent to good cosmetic results and the majority of adverse events have been low-grade. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Citation Format: Syed AMN, Chang H, Schwartzberg B, Bremner A, Boylan S, Lopez-Penalver C, Vito C, Davis M, Dooley W, Chakravarthy AB, Coomer C, Proulx G, Golder S, Ivanov O, Fernandez K, Farha MJ, Gonzalez V, Wengler C, Bhatnagar A, Neuner GA, Kopkash K, Rahman S, Costa P. A multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer: Early results of unplanned boost participants [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-20.

Development and Evaluation of a Prediction Model for Underestimated Invasive Breast Cancer in Women with Ductal Carcinoma In Situ at Stereotactic Large Core Needle Biopsy

BackgroundWe aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery.MethodsFrom the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization) and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration.Results348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7%) patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28), number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01), presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77), and microinvasion (OR 3.75, 95% CI 1.42-9.87). The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke’s R 2), mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73), and fairly good calibration.ConclusionThe evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.

A Method to Quantify Breast MRI for Predicting Tumor Invasion in Patients with Preoperative Biopsy- Proven Ductal Carcinoma in Situ (DCIS)

Dynamic contrast material-enhanced magnetic resonance imaging (DCE-MRI) can visualize alterations of vascularity and capillary permeability of breast lesions and enables us to identify breast lesions differentially from normal tissue (1-3). Owing to this characteristic of DCE-MRI, it has been widely used as INTRODUCTION �Received; June 30, 2012�Revised; March 22, 2013 �Accepted; March 22, 2013 Corresponding author : Sung Hun Kim, M.D. Department of Radiology, Seoul St. Mary’ Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea. Tel. 82-2-2258-6250, Fax. 82-2-599-6771 E-mail : rad-ksh@catholic.ac.kr A Method to Quantify Breast MRI for Predicting Tumor Invasion in Patients with Preoperative BiopsyProven Ductal Carcinoma in Situ (DCIS)

The Effect of Multiple Wire Localization in Breast Conservation

Variability exists regarding the surgical technique in breast conservation therapy. The purpose of this project was to determine differences between single (SH) or flanking (FH) hooked needle localization wires used for nonpalpable breast lesions. We retrospectively reviewed 201 female patients at a single institution from 2004 to 2008. All patients had biopsy-proven ductal carcinoma in situ or invasive disease. Comparisons were made in regard to margin status, reoperation, completion mastectomy, size of lesion, and breast specimen volume. SH was placed in 122 patients (61%) and FH in 79 patients (39%). In SH, 23 patients (18%) had positive margins and 31 patients (25%) had reoperations as compared with 31 patients (25%) with positive margin and 36 patients (44%) in the FH cohort (P = 0.039 and 0.0037). Average lesion size and volume resected was 1.5 cm and 137 cm(3) in SH and 2.85 cm and 188 cm(3) in FH, respectively (P = 0.0001 and 0.006). Positive margins were associated with lesion size and not volume of tissue excised. The FH technique was associated with more positive margins, reoperation, and completion mastectomy.

Diffusion-weighted magnetic resonance imaging in patients with known or suspected breast malignancy: Correlation between apparent diffusion coefficient and histopathologic diagnoses.

65 Background: Magnetic resonance imaging (MRI) is an important imaging modality for evaluating patients at high risk for breast malignancy. However, the role and utility of diffusion-weighted imaging (DWI) in breast MRI has not been fully elucidated. This study was designed to investigate the relationship between apparent diffusion coefficient (ADC) values and histopathologic diagnoses in benign and malignant breast pathologies as well as to assess the relative diagnostic value of this parameter. Methods: We searched our database for patients who received breast MRI studies from February 2010 through March 2011. We then identified those patients who had either known or suspected breast malignancy and who had also undergone DWI. Breast abnormalities were identified through a review of the short tau inversion recovery (STIR) and T1-weighted pre- and post-contrast images. DWI images were evaluated and the corresponding ADC values were calculated. These lesions were correlated with histopathologic results when available. Results: A total of 174 patient MRI studies were evaluated. Single dominant lesions were assessed and included biopsy-proven infiltrating ductal carcinoma (IDC), biopsy-proven ductal carcinoma in situ (DCIS), and benign lesions including cysts. The median ADC value for IDC was 118 x 10-5 mm2 s-1. The median ADC value for DCIS was 123 x 10-5 mm2 s-1. Finally, the median ADC value for breast cysts was 217 x 10-5 mm2 s-1. Conclusions: As the role of MRI continues to evolve in the evaluation of breast pathology, the addition of DWI may increase diagnostic confidence for breast cancer, allowing for further differentiation from benign lesions. DWI is feasible to implement in many clinical practices and correlates with imaging features of breast cancer. The DWI images are acquired rapidly and without intravenous contrast. This method of imaging could be used in short intervals to assess treatment response to therapies such as biologic inhibitors or radiation therapy.