e12586 Background: In patients undergoing mastectomy, the large raw surface from the dissection requires meticulous hemostasis to minimize surgical complications. Conventional electrosurgical coagulation (CEC) systems are a popular choice for dissection of the mastectomy flaps and for securing hemostasis. Argon beam coagulation (ABC) may allow for more rapid hemostasis which may impact blood loss, drain duration and drain output. The objective of this study is to evaluate device efficacy between the ABC and CEC for cutting and coagulation during mastectomy procedures with reconstruction. Methods: This single-institution, randomized trial consisted of consenting women undergoing unilateral or bilateral mastectomy and reconstruction. All enrolled subjects underwent mastectomy with immediate breast reconstruction and were randomized in a 1:1 fashion to either ABC or CEC. Each patient was followed for 2 months post-surgical drain removal and exited from the study. The study was powered to demonstrate the superiority of the ABC to CEC for post-mastectomy procedure time to hemostasis. Secondary outcomes measured included: blood loss, drainage duration, and total drain output. Statistical comparisons for time to hemostasis was made with mixed-effects analysis of variance. Blood loss, drainage duration and total drain output were compared using analysis of covariance, adjusted for bilateral or unilateral treatment. Results: A total of 82 patients were randomized (41 to ABC and 41 to CEC) between April 2021 and September 2024. Patients ranged in age from 26 to 80 years. Mastectomy with reconstruction was performed for a diagnosis of breast cancer in 68 patients (83%) and for risk-reduction in 14 patients (17%). There were 18 unilateral procedures (22%) and 64 bilateral procedures (78%). The patients underwent reconstruction as follows: tissue expander placement in 47 patients (57%), direct-to-implant in 7 patients (9%), deep inferior epigastric perforator flap in 27 patients (33%) and profunda artery perforator flap in 1 patient (1%). The primary and secondary endpoints are listed in Table 1. Post-mastectomy procedure time to hemostasis, was significantly different between ABC and CEC. Conclusions: In patients undergoing mastectomy with reconstruction, ABC shows improved time to hemostasis compared to CEC. There was no difference in secondary outcomes of blood loss, drainage duration and total drain output. Primary and secondary endpoints of ABC versus CEC. Endpoint Argon beam coagulation Conventional electrosurgical coagulation p -value Time to hemostasis (mins) 3.9 ± 3.9 6.9 ± 4.8 p < 0.001 Blood loss (mL) 126.0±81.0 173.1±260.8 p = 0.3 Drainage duration (days) 14.3±4.9 14.2±5.0 p = 0.9 Total drain ouput (mL) 1175±610 1168±770 p = 0.9

Background:Teaching and learning in the operating room environment are unique and impactful experiences. Little is known about effective and ineffective teaching methods. Our objective was to evaluate urology resident attitudes about aspects of teaching in the operating room that are helpful compared with those that are less effective. Materials and methods:Our mixed-methods analysis included written submitted evaluations of faculty by residents from our institution, as well as semi-structured interviews with trainees from different regions of the United States. We separated evaluations of faculty from 1 May 2013 to 30 April 2023 into highest and lowest quartiles based on numeric scores. We then conducted semi-structured interviews with trainees from institutions in different regions of the United States. Open-ended questions allowed participants to express themselves independently, and follow-up discussions explored their perception of effective methods of teaching in the operating room. All evaluations were printed and interviews transcribed. Three blinded, independent reviewers analyzed feedback to identify common themes associated with effective and ineffective teaching in the operating room. We analyzed transcripts using a multistage, cutting-and-sorting technique in an inductive approach based on grounded theory analysis. This work has been reported in line with the Consolidated criteria for Reporting Qualitative Research (COREQ) criteria. Results:Our analysis included 22 faculty (11 in each quartile) with an average of 16 evaluations each, as well as 20 transcribed interviews. Effective teaching involved clinician decision-making capability, specific communication, and appropriate graduated responsibility with patience. Ineffective teaching was characterized by poor decision making, lack of actionable communication/feedback, and absence of graduated autonomy/patience. Personal likeability was not a feature of effectiveness. Conclusion:Structured analysis of teaching methods in the operating room may allow continuous improvement for all teachers in the academic teaching mission. Further studies may explore consensus panels and potential creation of best practices that can help guide teachers and learners.

Abstract Background/Purpose: The use of superparamagnetic nanoparticles of iron oxide tracers (Magtrace) and electromagnetometers (SentiMag) for the detection of sentinel lymph nodes (SLN) during breast cancer surgery has been demonstrated to be noninferior to traditional radioisotope (RI) and blue dye detection, with additional safety benefits. Previous work has shown that transcutaneous detection of SLN with Magtrace/Sentimag is possible for over 30 days. Because of the safety, efficacy, and long detection window of Magtrace, we aim to investigate the use of Magtrace to prevent unnecessary SLN biopsies (SLNB) in breast cancer surgery. SLNB are commonly performed during breast conserving surgeries (BCS) or mastectomy for patients with a preoperative diagnosis of ductal carcinoma in-situ (DCIS). Because metastasis is not expected in patients diagnosed with DCIS, SLNB may be unnecessary and potentially harmful. However, in 15-25% of cases, unexpected invasive carcinoma is found during the post-surgical histopathological analysis of the resected breast tissue. For these cases, if SLNB are forgone during the initial surgery, SLNB during a second (delayed) procedure is the usual standard of care to evaluate SLN for metastasis. However, potential changes to lymphatic drainage following the initial resection may affect tracer localization to SLN. Consequently, we aim to compare SLN detection rates during delayed SLNB with Magtrace administered prior to initial BCS or mastectomy and subsequent RI tracer administered prior to delayed SLNB. Methods: SENTINOT2 is an ongoing international trial with BCM as the sole US site. For eligible patients with a preoperative diagnosis of DCIS, Magtrace will be administered prior to BCS or mastectomy. If invasive carcinoma is found from the post-surgical histopathological analysis, patients will receive delayed SLNB within 4 weeks of their initial surgery. Prior to delayed SLNB, patients will be randomized into two groups differing in the order of modality used for SLN detection (Magtrace or RI). Subjects with the following conditions will be excluded from the study: hypersensitivity to Magtrace, iron overload disease, pregnancy, and lactation. The total expected accrual for this study is 538 subjects globally and 50 subjects at BCM. Results: Currently, 19 patients have been enrolled in SENTINOT2. The subject population is 11% Asian, 26% Black/African American, and 47% Caucasian with non-Hispanic ethnicity. 5% of subjects identified as Hispanic Caucasian and 11% of subjects declined to report their race or ethnicity. 79% of patients had mastectomies, while 21% had BCS. After post-surgical histopathological analysis, 21% (4/19) patients were determined to have invasive carcinoma and received delayed SLNB. 50% (2/4) of these patients were randomized to have Magtrace as their first SLN detection modality (Mag-RI) while the other 50% (2/4) had RI as their first SLN detection modality (RI-Mag). Table 1 shows comparable SLN detection rates between Magtrace and RI for patients who received delayed SLNB. Only 1/4 patients showed SLN metastasis. For this patient, the positive SLN was successfully detected by both modalities. Conclusion: Magtrace has shown potential in delayed SLN detection and the use of Magtrace has prevented 79% (15/19) of enrolled patients from receiving unnecessary SLNB. Table 1. Number of Lymph Nodes (LN) Detected by Magtrace/Radioisotope, Biopsied and Positive for Metastasis Citation Format: Mary Bajomo, Ivan Marin, Jessica Montalvan, Margarita Riojas-Barrett, Logan Healy, Elizabeth Bonefas, Stacey Carter, Alastair Thompson. SENTINOT2- Use of superparamagnetic iron oxide tracer to avoid unnecessary sentinel lymph node biopsies [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 PO5-20-01.

Table depicting the study population

Plasma imlunestrant concentrations at visit 2

Abstract Background: Breast ultrasound (US) is a remarkable supplementary tool alongside mammography and magnetic resonance imaging (MRI) for the detection of breast lesions. US imaging is a fast, reliable method to identify and localize breast pathology. Innovative technologies that aim to timely identification and prompt diagnosis of suspicious lesions in breast cancer screening remain a clinical need. ATUSA is a B-type rechargeable US, shaped as a wearable device. It uses a linear array of transducers with water acting as a coupling medium that recreates a 3-dimensional image of the scanned breast. The ATUSA portability makes this device a practical breast screening method during a healthcare office visit. We report the initial feasibility of ATUSA to detect breast lesions in an outpatient setting from a trial in progress. Methodology: Interim prospective data from 35 female patients presenting with a mass of equal or greater than 1 cm in size, with a baseline handheld US image and pathology reports that evidenced a cancer diagnosis or a lesion suspicious of malignancy. Breast cancer types included invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), invasive mammary carcinoma (IMC) with mixed ductal and lobular features and atypical lobular hyperplasia (ALH). ATUSA and baseline handheld reference US images were cross-referenced from June 2022 to June 2023. Basic demographics, clinical characteristics, mammogram and/or MRI, and pathology reports were included in the analysis. Patients were followed up for a 30-day period to note occurrence of any adverse event (AE). Institutional Review Board (IRB) approved this study (protocol H-42616). Results: The 35 patients had a mean age of 57 years (range: 25 – 79), mean BMI 29.6 kg/m2 (range: 18.1 – 49.3). Mammographic breast density was fibroglandular tissue 15 (42.8%), followed by heterogeneously dense (HD) 13 (3.7%), mixed HD and fibroglandular 1 (2.8%), mildly dense 1 (2.8%), extremely dense 2 (5.7%), and extremely fatty 1 (2.8%). Breast sizes were 1 (2.8 %) A cup, 11 (31.4%) B cups, 1 (2.8%) B – C cups, 5 (14.2%) C cups, 1 (2.8%) C – D cups, 13 (37.1%) D cups, and 3 (8.5%) DD cups. The 35 scanned lesions had a diagnosis (compared with final resected pathology) classified as IDC 18 (51.4 %), DCIS 2 (5.7 %), mixed IDC and DCIS 6 (17.1 %), ILC 3 (8.5 %), IMC with mixed features 2 (5.7 %), IMC with DCIS 1 (2.8 %), ALH 1 (2.8 %), and 2 (5.7 %) benign masses. ATUSA successfully identified 17/35 (48.5 %) lesions from this group as malignant, from which 4 were hard to distinguish due to shadowing artifact and 3 were underestimated in size. A total of 15 (42.8 %) malignant lesions were missed by ATUSA. No AEs related to the ATUSA device were reported. Conclusion: The ATUSA provides the means to produce a good quality US image during a clinic visit or where a facility lacks conventional US imaging. When compared to the handheld US, ATUSA can be safely used in the outpatient setting without the need of trained specialists but requires further development and testing to match conventional breast imaging. Table 1. Basic clinical characteristics & demographics Citation Format: Margarita Riojas-Barrett, Jessica Montalvan, Mary Bajomo, Ivan Marin, Quan Dang Nguyen, Karla A Sepulveda, Elizabeth Bonefas, Alastair Thompson, Stacey Carter. A novel portable breast cancer screening method - initial institutional experience [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 PO5-19-11.

AbstractPurpose: Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study. Patients and Methods: Postmenopausal women with untreated, operable estrogen receptor (ER)–positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/posttreatment). Safety and pharmacokinetics were also assessed. Results: Among evaluable paired samples (n = 75), PD profiles demonstrated consistent ER targeting between 400- and 800-mg doses, with less toxicity at the 400-mg dose. Although inducing the lowest rate of complete cell-cycle arrest, PD and pharmacokinetic results were similar for the 200-mg dose. Conclusions: EMBER-2 combined with existing phase I data has identified 400 mg as the optimal imlunestrant dose.

Abstract Background/Purpose: The ConMed HelixAR Electrosurgical Generator with Argon Beam Coagulation Technology (CHEST) trial aims to focus on patients undergoing mastectomy, either unilateral or bilateral, with immediate breast reconstruction including breast implants, tissue expander placement, or autologous flap. The study design follows the standard of care procedure with device efficacy being measured between two devices regularly used in the operative setting: the HelixAR Electrosurgical Generator (HEG) and the Conventional Electrosurgical Coagulation (CEC) systems. The need for safe alternative surgical tools is increasing as the number of women needing surgical treatment increases. Allowing for the test and comparison of these standardized devices gives an extent to the advantages of using one over the other. To evaluate the device effectiveness between the HelixAR Electrosurgical Generator and Conventional Electrosurgical Coagulation systems for cutting and/or coagulation of tissue during mastectomy and reconstruction surgery, we report the implementation in a randomized clinical trial. The study is powered to show superiority of the HEG to the CEC as it relates to the primary objective of time from post-mastectomy to hemostasis. The HEG is designed to deliver argon gas and high frequency electrical current compared to the CEC delivering high frequency electrical current only. The primary efficacy measure is the time it takes from post-mastectomy to hemostasis with the secondary effectiveness endpoints being infection, drain duration, total drain output, blood loss and device related adverse events. The study hypothesizes that the time for post-mastectomy hemostasis is significantly less for the HEG than the CEC. Additional hypotheses include overall less device related adverse events, lower blood loss, and reduced operative time in favor of the HEG. Methods: This is a prospective 1:1 randomized controlled study of the HEG versus the CEC for patients undergoing a mastectomy with reconstruction procedure. 82 patients will be enrolled and distributed in two arms of 41 patients with a primary objective to assess the device efficacy for cutting and coagulation. The subject population includes patients with breast cancer or high risk from genetic mutations and/or family history. Exclusion factors include known history of bleeding diathesis or coagulopathy, advanced refusal of blood transfusion, active systemic or cutaneous infection or inflammation. The enrolled patients will be followed for 2 months post-operatively. Results: The study is open with 53/82 (65%) patients enrolled at the time of the abstract submission. Of those, 26 subjects were randomized to the CEC and 27 to the HEG. 27 subjects have experienced an adverse or serious adverse event including bruising, infections, and wound dehiscence, none determined to be related to the device use. For the study, analysis will focus on the primary endpoint comparing post–mastectomy procedure time to hemostasis between the two devices. Conclusion: The CHEST trial demonstrates the feasibility of conducting a randomized controlled trial at a single center in a complex operative setting comparing two surgical modalities. The testing of these surgical devices provides rationale for the implementation of safe and regulated clinical trials. While both devices are FDA approved and regularly used, the standardization of device efficacy is becoming more prevalent as new innovations get introduced into the surgical setting. Citation Format: Jessica Montalvan, Ivan Marin, Logan Healy, Margarita Riojas-Barrett, Mary Bajomo, Elizabeth Bonefas, Alastair Thompson, Marco Maricevich, Sebastian Winocour, Stacey Carter. Trial in progress: A prospective randomized, controlled study to evaluate device efficacy for cutting and/or coagulation of tissue during mastectomy procedures [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 PO5-19-09.

Introduction: Women 30 years-old or older that present with a breast complaint typically receive a standard work-up, which includes a diagnostic mammogram ultrasound. Because women under 30 years-old have extremely dense breast tissue, the initial imaging work-up begins with ultrasound. The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) describes and categorizes imaging findings using a standardized language to convey to non-radiologist physicians and patients the risk associated with a described breast lesion. Interpretation of the results can be problematic in young women (< 18 y.o) that may undergo imaging at a pediatric facility, often without on-site breast imaging specialists and standard breast imaging protocols in place, including the usage of the BI-RADS lexicon. Appropriateness of biopsy and surgical management require careful consideration especially in a setting where the pathology is often benign. We describe our 5-year experience of 482 young women undergoing breast imaging at a single institution to identify key features characteristic of young women with malignant lesions. Methods: A retrospective cohort study was conducted on all patients between the ages of 9-29 years old that presented to a breast imaging center for evaluation of a breast complaint from January 2017 through December 2021. Patients were identified via an Epic SlicerDicer query based on age and breast imaging procedure. A retrospective chart review was conducted on this cohort to capture demographic information (Table 1), medical history and family history. Information related to radiographic evaluation, biopsy procedures, and post-operative pathology was also recorded. Results: Four hundred-eight two patients with mean age of 23.8 3.7 years were seen for a breast complaint at the imaging center, of which 462 underwent breast ultrasound (96.7%). A BI-RADS classification was assigned in 418 reports (87%). Fifty-eight patients (12%) had imaging at an outside facility before coming to our dedicated breast imaging center. The mean maximal dimension at presentation was 1.3 1.6 cm. A BI-RADS classification of 4 was assigned to 46 patients (9.6%). A core needle biopsy (CNB) was performed in 63 patients (13.1%). Seventy-seven patients (16%) underwent surgery. Of the patients undergoing surgery, 38 (49.4%) had a CNB prior to surgery and the mean pre-operative maximal dimension on ultrasound was 3.1 1.6. Reason for excision included: mass size (30.3%), symptoms (27.6%), biopsy result (21.1%) and growth (19.7%). Eight patients (12.7%) were found to have a malignancy on CNB. Fibroadenoma (64.5%) was the most common pathology after surgery. A phyllodes tumor was identified in 8 patients, of which 6 were benign (7.9%) and 2 were classified as borderline (2.6%); there were no malignant phyllodes in the cohort. The mean size for phyllodes lesions were 3.8 1.8 cm. Six of 8 patients had a malignant lesion on final surgical pathology (7.9%); the other 2 patients achieved a pathologic complete response (pCR). Details regarding malignant lesions can be found in Table 2. Conclusions: While the American College of Radiology helps provide guidance for appropriate imaging evaluation in young women, there are no treatment algorithms that address the appropriateness of surgical treatment in this age group where the diagnosis is often benign. Radiologist and surgeons that specialize in breast disease may be asked to provide guidance on management decisions for a population they may rarely see (patients < 18 years-old), just as pediatrician or pediatric surgeons may feel pressure to making management plans for complaints they rarely encounter (breast). The value of using standardized imaging and treatment protocols with dedicated breast radiologist and surgeons may offer the best comprehensive approach to this unique subset of patients and deserves further evaluation. Table 1. Demographic and medical history. Values are n (%) or median [interquartile range]; BMI, body mass index Table 2. Characteristics of masses in young women. Values are n (%) or median [interquartile range].; *including juvenile fibroadenoma; **benign cyst, ductal ectasia, normal breast tissue, and papilloma; independent t-test was used to compare means for continuous variables; Pearson’s chi-squared test was used for categorical data; BMI, body mass index; NS, not significant Citation Format: Stephanie A. Ramirez, Brian A. Menegaz, Ashley Roark, Elizabeth Bonefas, Karla A Sepulveda, Alastair M. Thompson, Stacey Carter. Assessment and Diagnosis of Breast Pathology in Young Women: What Can We Learn? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-08.

Background: Imlunestrant is a novel, orally bioavailable selective estrogen receptor degrader (SERD) with pure antagonistic properties that result in sustained inhibition of estrogen receptor (ER)-dependent gene transcription and cell growth. In a phase 1 study, imlunestrant monotherapy showed favourable safety, pharmacokinetics (PK) and preliminary efficacy in heavily pre-treated ER-positive (ER+) advanced breast cancer patients (Jhaveri ASCO 2022). Here, we present pharmacodynamic (PD) data from the preoperative window of opportunity (WOO) study (EMBER-2, NCT04647487), evaluating the biological activity of imlunestrant monotherapy in ER+, HER2-negative (HER2-) early breast cancer (EBC). Methods: Post-menopausal women with stage I–III operable ER+ (>50%) or Allred score >5, HER2- untreated EBC ≥1 cm in diameter were randomized 1:1 to imlunestrant 400 mg once daily (QD) or imlunestrant 800 mg QD for 15 days (treatment window of -2 to +7 days) up to the surgery date. Pre- and on-treatment tumor samples were compared for changes in PD biomarkers. Primary study objective was change in ER expression (measured by IHC and quantified by H-score). Secondary objectives were change in progesterone receptor (PR) expression (measured by IHC and quantified by H-score) and Ki-67 (measured by IHC and expressed by percentage positive scoring) along with evaluation of safety and tolerability. Results: From Apr 28, 2021, to Mar 11, 2022, 58 patients were enrolled of which 54 were biomarker-evaluable for ER expression (400 mg: n = 28; 800 mg: n = 26). Patient demographics and tumor characteristics for all enrolled patients were similar across cohorts, with a median age of 64 years (50-83), 72% invasive ductal carcinoma (IDC), 28% invasive lobular carcinoma (ILC), 59% stage I, 36% stage II and 5% stage III disease. 91% of the patients had a compliance rate higher than 80%. Among biomarker evaluable patients, relative reduction in PD biomarkers after a median of 15 days (range 13 to 23 days) of treatment are presented in Table 1. There was no significant difference in PD biomarker modulation noted between the two imlunestrant doses (400 mg vs 800 mg) or based on tumor histology (IDC, ILC). Imlunestrant was well tolerated. There were no discontinuations due to adverse events (AEs). Treatment-related AEs (TRAEs) were mainly grade 1, most commonly: fatigue (10%), diarrhea (9%), hot flushes (7%), and nausea (5%). There were no TRAEs of diarrhea and nausea observed at the 400 mg dose. No grade 3 or higher TRAEs were reported. Conclusion: Imlunestrant demonstrated evidence of target engagement along with consistent biological activity across all evaluated dose levels and was well tolerated in an EBC population, further supporting continued adjuvant development in the ongoing EMBER-4 study. Additional biomarker analyses for the EMBER-2 study are also planned. Table 1. Relative reduction in PD biomarkers from Baseline to Day 15 Citation Format: Patrick Neven, Nicole Stahl, Maria Vidal, Miguel Martín, Nadia Harbeck, Peter A. Kaufman, Francois-Clement Bidard, Peter A. Fasching, Philippe Aftimos, Erika Hamilton, Stacey Carter, Peter Schmid, Duncan Wheatley, Manali Bhave, Kelly K. Hunt, Swati A. Kulkarni, Roohi Ismail-Khan, Claudia Karacsonyi, Shawn T. Estrem, Umut Ozbek, Bastien Nguyen, Eva Ciruelos. A preoperative window-of-opportunity study of imlunestrant in estrogen receptor-positive, HER2-negative early breast cancer: Results from the EMBER-2 study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-06.

Background/Purpose: Superparamagnetic iron oxide (SPIO)-based techniques like Magseed and Magtrace offer alternatives for breast lesion and sentinel lymph node (SNL) localization. Magseeds placed under ultrasound guidance offer logistical and safety advantages compared to traditional wire-localization or radioactive seed placement. Further, Magtrace injection is a viable SNL-localization alternative that overcomes radiation safety, skin necrosis, and allergic reactions associated with traditional 99mTc colloid and Methylene blue/Isosulfan blue dyes. To evaluate the effectiveness of these techniques in surgical practice, we report the implementation of Magseed and Magtrace at Baylor St. Luke’s Medical Center. Methods: We retrospectively reviewed prospectively collected data from the 128 female patients undergoing Magseed/Magtrace procedures from October 2019 to December 2020. Demographics and clinical characteristics were summarized, and surgical outcomes analyzed including margin status, re-excision rates, post-operative breast and axilla complications, successful localization and detection rates. Results: Patients presented with varied diagnoses including 98 (77%) with invasive carcinoma, 21 (16%) with DCIS, and 9 (7%) with fibroadenoma, papillary, or other lesions. 50 patients (39%) underwent neoadjuvant therapy. Mean BMI at surgery was 27.33 kg/m2 (range, 17.80-48.65) and mean age was 57.26 years (range, 27-86). Breast density varied, 5 (4%) categorized as almost entirely fatty, 69 (54%) as heterogeneously dense, 12 (9%) as extremely dense, and 39 (30%) with fibroglandular density. For breast size there were 2 (2%) A cups, 13 (10%) B cups, 16 (13%) C cups, 10 (8%) D cups, 8 (6%) DD cups, 2 (2%) DDD cups, 1 (.8%) F cup, and 12 (9%) with in between breast size (A-DDD). 108 patients (84%) had on-table Magtrace injection and 52 (41%) had Magseed localization. 18 (14%) patients had Methylene blue/Isosulfan blue dye or Technetium-99 used with Magseed and/or Magtrace. There was a 100% (52/52) success rate of lesion localization using Magseed and a 94% (101/108) success rate of SLN detection using Magtrace. Magtrace brown skin staining occurred in 12/108 patients (11%). Breast complications occurred in 43 patients (34%), with bruising/hematoma in 30/43 (70%), seroma in 7/43 (16%), and infection in 4/43 (9%). Axilla complications occurred in 11 patients (9%): 5/11 (45%) had bruising/hematoma, 6/11 (55%) had seroma, and 1/11 (9%) had infection. Positive margins were seen in 11 (9%) patients with re-excision performed in 8 women (6%). Conclusions: Magseed and Magtrace are comparable to standard practices in terms of practicality, surgical implementation, and risk of surgical complications and re-excision, providing a rationale for the adoption of SPIO-based techniques. By putting these surgical techniques into practice and evaluating their success in excising a wide range of lesions and monitoring complications, there is possibility of introducing new, innovative techniques into a standardized clinical setting within surgical oncology. Magseed/Magtrace Procedures at BSLMCRaw NumberPercentageTechniquesMagtrace Only6047%Magseed Only1915%Magtrace + Magseed3124%Isotope1713%Blue Dye11%Skin Staining Post-Op.1211%Breast Complication4334%Wound Complication921%Infection49%Bruising/Hematoma3070%Seroma716%Patients with >1 complication49%Axilla Complication119%Wound Complication00%Infection19%Bruising/Hematoma545%Seroma655%Patients with >1 complication19%Re-excision Rate86%Histological TypesER+, HER2-7055%ER+10078%HER2+2016%TNB1310% Citation Format: Jessica Montalvan, Logan Healy, Huma Javaid, Ivan Marin, Brian Menegaz, Cary Hsu, Eric Silberfein, Elizabeth Bonefas, Stacey Carter, Alastair Thompson. Magseed/magtrace-guided surgery in breast cancer- an institutional perspective [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 P3-20-06.

Abstract DCIS is traditionally viewed as a surgical problem managed in a comparable way to invasive breast cancer, by breast conservation or mastectomy, to prevent the evolution of intraductal to invasive disease. The need for surgery has been challenged by retrospective case series demonstrating that progression from DCIS to invasive disease is variable, increases with time, but may be modified by endocrine therapy. This data has led to the innovative trials currently under way of active monitoring compared with surgery – the “if” of whether surgery is needed. What surgery to perform requires pathology confirmation of the diagnosis, awareness of the heterogeneity of DCIS (and the potential for sampling to miss invasive disease) together with imaging by mammography, ultrasound and/or MRI. Clinical impressions, imaging and pathology findings direct treatment options. Surgery comprises lumpectomy versus simple, skin sparing or nipple sparing mastectomy (with consideration for reconstruction) potentially partnered with axillary node surgery, at least for those undergoing mastectomy. When (and how) to perform surgical and allied techniques is undergoing change. The required surgical margins of 2mm (for pure DCIS) at the time of conservation to reduce local recurrence remains challenging, with technologies such as optical coherence tomography demonstrating promise for intraoperative determination of adequate margins. Rather than routine sentinel lymph node biopsy, with the attendant risks of lymphedema, iron oxide/dextran coated particles injected prior to surgery, rapidly migrate to and lodge in the axillary nodes and provide an option for delayed axillary surgery if invasive disease is identified. Neoadjuvant approaches to DCIS, targeting the estrogen receptor or HER2, to downstage the extent of surgery are less favored than for invasive breast cancers, but DCIS may be the residue left after neoadjuvant treatment for invasive disease. However, adjuvant endocrine therapy and adjuvant radiotherapy may each have an impact on reducing the chance of re-occurrence of DCIS or development of invasive cancer. Currently, surgery remains the primary treatment for DCIS. If surgery is performed, what is done and when surgery takes place varies with the nature, the extent of the DCIS and is influenced by patient preference. Citation Format: Alastair M. Thompson, Elizabeth Bonefas, Stacey Carter, Ivan marin, Huma Javaid, Jessica Montalvan. Surgery for DCIS: If, what and when [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 IA019.

BACKGROUND Intraoperative tissue analysis and identification are critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and evaluation of the MasSpec Pen technology for molecular analysis of in vivo and freshly excised tissues in the operating room (OR). METHODS An Orbitrap mass spectrometer equipped with a MasSpec Pen interface was installed in an OR. A "dual-path" MasSpec Pen interface was designed and programmed for the clinical studies with 2 parallel systems that facilitated the operation of the MasSpec Pen. The MasSpec Pen devices were autoclaved before each surgical procedure and were used by surgeons and surgical staff during 100 surgeries over a 12-month period. RESULTS Detection of mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries was achieved. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. CONCLUSIONS This study shows that the MasSpec Pen system can be successfully incorporated into the OR, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be used to inform surgical and clinical decisions without disrupting tissue analysis workflows.

Intraoperative tissue analysis is critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and intraoperative use of the MasSpec Pen technology for direct molecular analysis of in vivo and freshly excised tissues in the operating room. In this study, the MasSpec Pen was used by surgeons and surgical staff during 100 surgeries over a 12-month period, allowing rapid detection of rich mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. Collectively, this study shows that the MasSpec Pen system can be successfully incorporated into the operating room, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be inform surgical and clinical decisions without disrupting tissue analysis workflows.

Abstract Complete tumor removal during breast conserving surgery (BCS) remains a challenge for even the most experienced surgeons due to difficulties associated with detecting residual disease at the margin. Additionally, there is limited technology to evaluate resected tissue while the patient is under anesthesia. Mass spectrometry (MS) has been previously used for rapid molecular characterization of healthy and diseased tissue and has shown potential for intraoperative use. We have developed an MS-based technology that couples a handheld and biocompatible device, the MasSpec Pen, to a mass spectrometer for non-destructive ex vivo and in vivo analysis of cancer tissue in a matter of seconds. We have used the MasSpec Pen with multivariate statistical analysis to discriminate the molecular patterns of normal breast and lymph node from invasive cancer tissue, achieving accuracies over 88%. Our results showcase the potential of the MasSpec Pen to provide surgical guidance during BCS. A total of 213 banked human tissues including normal breast and lymph node, IDC, and IDC to lymph node were obtained from the Cooperative Human Tissue Network and stored at -80°C prior to analysis. Samples were then thawed and analyzed using a mass spectrometer coupled to the MasSpec Pen. During MasSpec Pen analysis, a single water droplet is held in contact with the tissue to extract molecules that are then analyzed by a mass spectrometer, yielding a molecular fingerprint. The molecular information obtained is analyzed by the statistical model to provide a predictive diagnosis in seconds. The least absolute shrinkage and selection operator (Lasso) statistical method was used to generate predictive models comprised of molecular features indicative of healthy and diseased tissue. Analyzed regions of tissue were demarcated with a surgical ink marker, snap frozen, and sectioned at a thickness of 5µm. Tissue sections were H&E stained for pathological evaluation. The MasSpec Pen was used to analyze 79 normal and 64 breast cancer tissues. Various molecular species involved in cell metabolism, including metabolites, fatty acids, and glycerophospholipids were observed in the mass spectra. For example, glutamate was detected at a high relative abundance in breast cancer tissue while hexose was detected at a high abundance in normal breast tissue. The primary breast cancer model yielded a sensitivity and specificity over 95% for the training set (n=68) and validation set (n=22). The diagnostic capabilities of the model were further evaluated by predicting on an independent test set of samples (n=53). A sensitivity and specificity of 83.9% and 100% were achieved, demonstrating the ability of the MasSpec Pen to discriminate between normal and cancerous breast tissue. The MasSpec Pen was used to detect metastatic breast cancer in lymph node. Normal lymph nodes (n=26) and nodes with metastatic disease (n=44) were analyzed with the MasSpec Pen. For the metastatic breast cancer model, overall accuracies of 88.7% and 94.1% were achieved for the training set (n=46) and validation set (n=17), respectively. We envision the MasSpec Pen to be used in the operating room (OR) for the in vivo analysis of breast cancer. Recently, we have implemented the MasSpec Pec in the OR to evaluate the feasibility of this technology for intraoperative analysis of breast and lymph node tissue. Similar molecular species are detected in spectra obtained from the in vivo and ex vivo analysis of human breast and lymph node tissue when compared to spectra obtained from banked tissue. Continuous effort is being made to continue patient accrual and testing of the technology. Collectively, these results showcase the capability of the MasSpec Pen for breast cancer detection and its potential as an intraoperative tool for rapid breast cancer diagnosis and surgical margin evaluation during BCS. Citation Format: Kyana Y Garza, Jialing Zhang, John Q Lin, Stacey Carter, James Suliburk, Chandandeep Nagi, Livia S Eberlin. Advanced development of the MasSpec Pen technology to aid in breast cancer surgical margin evaluation and diagnosis during surgery [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 P1-20-04.