High-risk Breast Lesions Research Articles

Engaging Multidisciplinary Teams to Develop Pragmatic Clinical Practice Guidelines to Support Management of Patients With High-Risk Breast Lesions

IntroductionWe sought to develop clinical guidelines within our multidisciplinary Breast Center to support decision-making for managing high-risk breast lesions. The objective is to describe the process used to develop these guidelines and assess perceived acceptability. MethodsWe recruited clinical stakeholders to identify key “high-risk” topics. Stakeholder groups (surgery, radiology, pathology) met separately to review the topics, leveraging existing literature reviews and best available evidence. Guidelines were initially developed in 2015 and updated in 2019. We surveyed breast clinical team members in 2023 regarding the perceived acceptability of the guidelines and summarized the data. ResultsWe created clinical guidelines to address the management of atypical ductal hyperplasia, flat epithelial atypia, atypical lobular hyperplasia/lobular carcinoma in situ, radial scar/complex sclerosing lesion, and papillomas. Key guideline components included process for radiologic-pathologic correlation, patient disposition after biopsy (surgical referral needed, follow-up imaging recommended), recommendation for the role of surgical excision, and recommendation regarding imaging follow-up if excision not performed. Forty clinical team members (66% [40/60] response rate) completed the acceptability survey from varied disciplines. Most (78%) were aware of the guidelines. Respondents rated the recommendations for disposition after biopsy, surgical management, and follow-up imaging as the most helpful components. Most (> 80%) rated them to be very/extremely useful. ConclusionWe leveraged input from key stakeholders to develop clinical guidelines to support the multidisciplinary management of patients with high-risk breast lesions. Our guidelines have been successfully implemented across our academic and community practice. Future steps will assess the impact of implementation on clinical outcomes.

Accuracy of distinguishing benign, high-risk lesions and malignancies with inductive machine learning models in BIRADS 4 and BIRADS 5 lesions on breast MR examinations

Rationale and ObjectivesThe aim of this study is to explore the utility of Inductive Decision Tree models (IDTs) in distinguishing between benign, malignant, and high-risk (B3) breast lesions. Materials and MethodsWe analyzed 124 histologically confirmed lesions in 114 patients who underwent breast MR with BI-RADS 4 or 5 assessment. The dataset comprised 10 imaging parameters and one clinical observation. Using the IDTs method (algorithm C5.0) combined with the data balancing method SMOTE (Synthetic Minority Oversampling Technique) and a corresponding new method called LCC (Leveling of Cases per Class), we developed corresponding 3-class classification models (Benign, B3, or Malignant). The training set used for classification model development consists of 112 cases with 11 variables, and the model’s performance was assessed using 10-fold Cross-Validation and Leave One Out methods (utilizing the training set) and the Use Test Set method (testing on an unknown (for the models) dataset of 12 cases with 12 variables). ResultsThis preliminary study demonstrates the potential for IDTs to accurately distinguish between benign, B3 and Malignant lesions based on extracted data from breast MRI exams with a high classification accuracy (88.70%), mean sensitivity of 97.18% and specificity of 98.59% achieved by the optimal classification model, derived from the combination of the IDTs method and the LCC data balancing method. ConclusionThe present study represents a pioneering approach for three-category classification of breast lesions in MRI images using Artificial Intelligence (AI) which can be utilized as second-opinion tool in daily clinical practice by radiologists.

Use of web-based decision support to improve informed choice for chemoprevention: a qualitative analysis of pre-implementation interviews (SWOG S1904)

BackgroundWomen with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.MethodsThe parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. Interviews sought to understand attitudes/beliefs and barriers/facilitators to chemoprevention.ResultsInterviews with 25 providers (18 physicians and 7 advanced practice providers) were included. Providers were predominantly female (84%), white (72%), and non-Hispanic (88%). Nearly all providers (96%) had prescribed chemoprevention for eligible patients. Three themes emerged in qualitative analysis. The first theme describes providers’ confidence in chemoprevention and the utility of decision support tools. The second theme elucidates barriers to chemoprevention, including time constraints, risk communication and perceptions of patients’ fear of side effects and anxiety. The third theme is the need for early implementation of decision support tools.ConclusionsThis qualitative study suggests that providers were interested in the early inclusion of decision aids (DA) in their chemoprevention discussion workflow. The DAs may help overcome certain barriers which were elucidated in these interviews, including patient level concerns about side effects, clinic time constraints and difficulty communicating risk. A multi-faceted intervention with a DA as one active component may be needed.Trial registrationThis trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT04496739.

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention.

This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care.

ASO Visual Abstract: Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

ASO Visual Abstract: Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

Navigating breast health: a comprehensive approach to atypical ductal hyperplasia of the breast management and surveillance

Atypical ductal hyperplasia (ADH) is a benign lesion of the breast that is associated with an increased risk of invasive breast cancer. This review explores the pathophysiology, risk factors for progression to breast cancer, and lifetime management for patients diagnosed with ADH on core needle biopsy (CNB). The management plan for patients diagnosed with ADH includes regular clinical surveillance, diagnostic mammography, along with risk-reduction strategies such as lifestyle modifications or the use of adjuvant endocrine therapies. This review aims to delve into the complexities of ADH from diagnosis to management to aid clinicians in finding the best way to approach this high-risk breast lesion.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Retained Biopsy Site Markers After Breast Lesion Surgical Resection: Associations With Residual Malignancy.

BACKGROUND. Biopsy site markers (BSMs) placed during image-guided core needle biopsy (CNB) are typically targeted for surgical excision, along with the breast imaging abnormality. Retained BSMs raise concern of incomplete resection of the breast abnormality. OBJECTIVE. The purpose of our study was to assess the frequency of residual malignancy in patients with retained BSMs identified on the initial mammography performed after breast lesion surgical excision. METHODS. This retrospective study included 30 patients (median age, 59 years) who underwent surgical resection between August 2015 and April 2022 of a borderline, high-risk, or malignant breast lesion after CNB and technically adequate preoperative image-guided localization, in whom the initial postoperative mammography report described a retained nonmigrated BSM. EMR data were extracted. The index pathology from CNB and initial surgical resection was classified as malignant or nonmalignant. The presence of residual malignancy after initial surgical resection required pathologic confirmation from subsequent tissue sampling; the absence of residual malignancy required 2 years of benign imaging follow-up. RESULTS. Thirteen specimen radiographs were interpreted intraoperatively by a surgeon with later radiologist interpretation, and 17 underwent real-time radiologist interpretation. Eighteen patients had malignant index pathology from the initially resected lesion. The frequency of residual malignancy on subsequent follow-up after initial surgical resection was higher in patients with malignant than nonmalignant index pathology (39% [7/18] vs 0% [0/12], respectively; p = .02). Among patients with malignant index pathology, the frequency of residual malignancy was higher in those without, than with, malignancy in the initial surgical specimen (80% [4/5] vs 23% [3/13]; p = .047). Also in these patients, the frequency of a positive interpretation of the initial postoperative mammography (BI-RADS category 4 or 6) was not significantly different between those with and without residual malignancy (57% [4/7] vs 55% [6/11]; p > .99). CONCLUSION. Patients with retained BSMs associated with malignant index lesions are at substantial risk of having residual malignancy. Initial postoperative mammography is not sufficient for excluding residual malignancy. CLINICAL IMPACT. Retained BSMs associated with index malignancy should be considered suspicious for residual malignancy. In this scenario, timely additional tissue sampling targeting the retained BSM is warranted, given the greater-than-2% chance of malignancy. Active surveillance is a reasonable management strategy in patients with retained BSMs from nonmalignant index lesions.

Comparing Breast Cancer and Cardiovascular Disease Risk and Use of Chemoprevention and Statins among Women with High-risk Breast Lesions.

Among women with high-risk breast lesions, mean absolute risk of breast cancer was higher compared with cardiovascular disease; however, statin use was significantly higher than chemoprevention. To address underutilization of breast cancer chemoprevention, these drugs should be placed in the context of medications used to prevent other chronic diseases.

Long-Term Follow-Up of High-Risk Breast Lesions at Vacuum-Assisted Biopsy without Subsequent Surgical Resection

Introduction: B3-lesions of the breast are a heterogeneous group of neoplasms, associated with a higher risk of breast cancer. Recent studies show a low upgrade rate into malignancy after subsequent open surgical excision (OE) of most B3-lesions when proven by vacuum-assisted biopsy (VAB). However, there is a lack of long-term follow-up data after VAB of high-risk lesions. The primary aim of this study was to demonstrate whether follow-up of B3 lesions is a beneficial and reliable alternative to OE in terms of long-term outcome. The secondary aim was to identify patient and lesion characteristics of B3 lesions for which OE is still necessary. Methods: This retrospective multicenter study was conducted at 8 Swiss breast centers between 2010 and 2019. A total of 278 women (mean age: 53.5 ± 10.7 years) with 286 B3-lesions who had observation only and who had at least 24 months of follow-up were included. Any event during follow-up (ductal carcinoma in situ [DCIS], invasive cancer, new B3-lesion) was systematically recorded. Data from women who had an event during follow-up were compared with those who did not. The results for the different B3 lesions were analyzed using the t test and Fisher’s exact test. A p value of <0.05 was considered statistically significant. Results: The median follow-up interval was 59 months (range: 24–143 months) with 52% (148/286) having a follow-up of more than 5 years. During follow-up, in 42 women, 44 suspicious lesions occurred, with 36.4% (16/44) being invasive cancer and 6.8% (3/44) being DCIS. Thus, 6.6% (19/286) of all women developed malignancy during follow-up after a median follow-up interval of 6.5 years (range: 31–119 months). The initial histology of the B3 lesion influenced the subsequent occurrence of a malignant lesion during follow-up (p < 0.038). The highest malignancy-developing rate was observed in atypical ductal hyperplasia (ADH) (24%, 19/79), while all other B3-lesions had malignant findings ipsi- and contralateral between 0% and 6%. The results were not influenced by the VAB method (Mx-, US-, magnetic resonance imaging-guided), the radiological characteristics of the lesion, or the age or menopausal status of the patient (p > 0.12). Conclusion: With a low risk of <6% of developing malignancy, VAB followed by long-term follow-up is a safe alternative to OE for most B3-lesions. A higher malignancy rate only occurred in ADH (24%). Based on our results, radiological follow-up should be bilateral, preferable using the technique of initial diagnosis. As we observed a late peak (6–7 years) of breast malignancies after B3-lesions, follow-up should be continued for a longer period (>10 years). Knowledge of these long-term outcome results will be helpful in making treatment decisions and determining the optimal radiological follow-up interval.

Implementation of vacuum-assisted excision as a management option for benign and high-risk breast lesions.

Previous studies have shown that vacuum-assisted excision (VAE) is a safe and effective alternative for surgical excision (SE) of benign breast lesions. However, the use of VAE in high-risk lesions is controversial and guidelines are ambiguous. This study describes the impact of the implementation of VAE in terms of management and outcomes compared to a cohort before implementation. A single centre retrospective study with two cohorts: 'before' and 'after' implementation of VAE was performed. All patients with a benign or high-risk lesion treated by VAE or SE between 2016 and 2019 were included. Excision, complication, and upgrade rates were compared between both cohorts. Cox regression was used for the evaluation of recurrences and re-excisions. The overall excision rate of all benign and high-risk lesions was comparable in both cohorts (17% vs 16%, p = 0.700). After implementation, benign lesions were significantly more often managed by VAE (101/151, 67%, p < 0.001). Re-excision, recurrence, and complication rates were low and comparable between cohorts (4.3% vs 3.9%, p > 0.999; 3.0 vs 2.0%, p = 0.683; 3.4 vs 6.6%, p = 0.289, respectively). SE could safely be replaced by VAE in 58% of patients treated for a benign or high-risk lesion. With this shift in management, the use of operating rooms and general anaesthesia can safely be omitted in this patient group. Further research on high-risk lesions is warranted since our data are exploratory. This study provides supportive data for the use of VAE as a management option for both benign (up to 5 cm) and high-risk lesions. Outcomes on re-excision, recurrence should be confirmed in prospective studies especially in high-risk lesions.

Intercellular hif1α reprograms mammary progenitors and myeloid immune evasion to drive high-risk breast lesions.

The origin of breast cancer, whether primary or recurrent, is unknown. Here, we show that invasive breast cancer cells exposed to hypoxia release small extracellular vesicles (sEVs) that disrupt the differentiation of normal mammary epithelia, expand stem and luminal progenitor cells, and induce atypical ductal hyperplasia and intraepithelial neoplasia. This was accompanied by systemic immunosuppression with increased myeloid cell release of the alarmin S100A9 and oncogenic traits of epithelial-mesenchymal transition, angiogenesis, and local and disseminated luminal cell invasion in vivo. In the presence of a mammary gland driver oncogene (MMTV-PyMT), hypoxic sEVs accelerated bilateral breast cancer onset and progression. Mechanistically, genetic or pharmacologic targeting of hypoxia-inducible factor-1α (HIF1α) packaged in hypoxic sEVs or homozygous deletion of S100A9 normalized mammary gland differentiation, restored T cell function, and prevented atypical hyperplasia. The transcriptome of sEV-induced mammary gland lesions resembled luminal breast cancer, and detection of HIF1α in plasma circulating sEVs from luminal breast cancer patients correlated with disease recurrence. Therefore, sEV-HIF1α signaling drives both local and systemic mechanisms of mammary gland transformation at high risk for evolution to multifocal breast cancer. This pathway may provide a readily accessible biomarker of luminal breast cancer progression.

Radiological Society of North America (RSNA) 3D Printing Special Interest Group (SIG) clinical situations for which 3D printing is considered an appropriate representation or extension of data contained in a medical imaging examination: breast conditions

The use of medical 3D printing has expanded dramatically for breast diseases. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides updated appropriateness criteria for breast 3D printing in various clinical scenarios. Evidence-based appropriateness criteria are provided for the following clinical scenarios: benign breast lesions and high-risk breast lesions, breast cancer, breast reconstruction, and breast radiation (treatment planning and radiation delivery).

Abstract P5-04-06: Breast Imaging Recommendations for Females &amp;lt;40 Years of Age with ≥20% Lifetime Breast Cancer Risk: Practice Patterns at a Specialized Clinic

Abstract Background— There are limited data to guide breast cancer screening recommendations among females &amp;lt; 40 yrs of age with elevated lifetime breast cancer risk not driven by a known germline mutation. The American Cancer Society recommends initiating screening at age 30, while the National Comprehensive Cancer Network (NCCN) recommends 10 yrs younger than the youngest affected relative (YAR). Both support screening MRI in addition to annual mammogram (MMG). This study describes practice patterns related to screening imaging recommendations and patient (pt) follow-through in young females with ≥20% lifetime breast cancer cared for in a specialized clinic. Methods— At the Brigham and Women’s Hospital high-risk breast clinic, specialized advanced practice providers, surgeons and oncologists perform risk assessment including use of the Tyrer-Cuzick (TC) risk model, and provide risk management recommendations. For this study, we identified pts age&amp;lt; 40 yrs with &amp;gt;20% lifetime breast cancer risk, no known genetic mutation or high-risk breast lesions, and ≥1 first or second-degree relatives (FDR or SDR) with breast cancer. We evaluated factors associated with recommendation for i) early screening initiation, defined as prior to age 40, and ii) use of supplemental imaging modalities. Results—335 pts met study criteria: 20% were age&amp;lt; 30, 36% were 30-34, and 44% were 35-39. Mean lifetime risk by the TC model was 32% (SD: 10%). Early screening was recommended in 75%; these pts were more likely to have an affected FDR (71% vs. 48%, p&amp;lt; 0.001) and younger affected relatives (median age of YAR: 44 vs. 55, p&amp;lt; 0.001). Among pts whose YARs were age&amp;lt; 50, early screening was recommended in-line with NCCN guidelines for 99% of pts with FDRs&amp;lt; 50 vs. 80% of pts with only SDRs&amp;lt; 50 (p&amp;lt; 0.001). Among pts whose YARs were age≥50, early screening was recommended contrary to NCCN guidelines in 51%. Factors associated with an early screening recommendation in this subgroup were having received a prior MMG (62% recommended early screening vs. 33% with no prior MMG) as well as being older at time of risk discussion (median age 37 in early screening group vs. 34 in routine screening group) and having younger affected relatives (median age of YAR: 53 vs. 56) (all p≤0.01). Regarding use of supplemental imaging, 35% were recommended screening MMG alone, while 65% were also offered screening MRI or ultrasound (US). Factors most strongly associated with offering MRI/US included having heterogeneously or extremely dense breasts, normal BMI, greater extent of family history, younger affected relatives and higher TC scores (Table). All except extent of family history remained statistically significant in multivariable analysis. Among those offered supplemental MRI/US who were eligible to initiate screening, 48% had pursued MRI, 7% US +/- MRI, 27% MMG alone, and 18% had no screening imaging at a median follow-up of 17 months. Conclusions— These data suggest that providers in our high-risk breast clinic are using nuanced clinical judgment related to screening recommendations in pts &amp;lt; 40 yrs with elevated lifetime risk. Those with affected FDRs at age&amp;lt; 50 were consistently recommended early screening initiation, while practice recommendations varied more for pts with only SDRs age&amp;lt; 50 or those with YAR age≥50, suggesting a need for consensus criteria as to when to initiate screening in these subgroups. Multiple factors impacted recommendations for screening MRI/US, most notably breast density. Factors associated with offering supplemental screening with MRI/US Citation Format: Alexandra Wehbe, Alison Laws, Fisher Katlin, Eshita Sharma, Marybeth Hans, Mary Graichen, Brittany Bychkovsky, Rochelle Scheib, Judy Garber, Lydia Pace, Tari King. Breast Imaging Recommendations for Females &amp;lt;40 Years of Age with ≥20% Lifetime Breast Cancer Risk: Practice Patterns at a Specialized Clinic [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 P5-04-06.

Abstract P2-02-02: Phase I trial of the safety and immunogenicity of a tri-antigen vaccine targeting HER2, IGFBP-2, and IGF-IR in patients with non-metastatic breast cancer

Abstract Background: HER2, IGFBP-2, and IGF-IR are proteins that are overexpressed in breast cancer. These three proteins, when used as immunogens, provide broad antigenic coverage to all molecular breast cancer subtypes. The proteins are also up-regulated in pre-invasive and high-risk breast lesions which are associated with progression to invasive cancer. Therefore, generating protective immunity against these antigens could have the result of preventing cancer development in high risk patients. We identified epitopes derived from these proteins, termed Th1 selective epitopes, that specifically stimulated T-helper 1 immune responses in humans and mice. The tri-antigen vaccine was effective in preventing the development of breast cancer in a transgenic mouse model of neu-expressing mammary cancer. We conducted a dose finding study of a plasmid-based vaccine encoding three extended Th1 selective epitopes derived from these antigens in breast cancer patients. Methods: Patients with non-metastatic, node positive, HER2 negative breast cancer that are in remission and defined as no evidence of disease were enrolled sequentially to one of 3 dose arms: 150, 300, and 600 mcg of the tri-antigen vaccine plasmid with 10 evaluable patients per arm (NCT02780401). Vaccines were given monthly intradermally for three total doses with rhu-GM-CSF (100mcg) as an adjuvant. The primary endpoint was safety through the 6-month follow-up visit and the secondary endpoints were immunogenicity, persistence of the immune response after vaccination, and assessment of potential stimulation of T-regulatory (T-reg) cells or myeloid derived suppressor cells to the overexpressed non-mutated antigens as well as determining the recommended Phase II dose. Results: Thirty-two patients were enrolled and 97% received all three vaccinations. The mean age at enrollment was 51.9 years with 61% of patients being pre-menopausal and 39% post-menopausal. The majority of patients were Stage II/III. Eighty-eight percent of patients had hormone receptor positive tumors and twelve percent were triple negative disease. The majority of adverse events (AE) (&amp;gt;95%) were grade 1 or 2. The most common AE were injection site reactions, flu like symptoms, fatigue, chills, myalgia, and nausea. All doses were immunogenic with the greatest magnitude antigen specific Type I immune responses seen in the low and intermediate doses. Eighty percent of patients at the 300mcg dose retained high levels of antigen specific immunity at 1 and 6 months after immunization as compared to 57% and 50% at the 100 and 600mcg doses respectively. No antigen specific Th2 cells, MDSC or T-reg were generated with vaccination. Immunizations did not upregulate PD-1 on CD4 or CD8 T-cells. Conclusions: A plasmid-based vaccine encoding extended Th1 selective epitopes derived from HER2, IGFBP-2, and IGF-IR could be administered safely and generate high levels of antigen specific interferon gamma secreting T-cells (Th1). The 300mcg dose elicited significant immune responses in the majority of patients which persisted at least 6 months after the end of immunization. A Phase II study of the vaccine given in the neoadjuvant setting to patients with HER2 positive breast cancer is ongoing (NCT04329065). Citation Format: Sasha E. Stanton, Kari B. Wisinski, William R. Gwin, Andrew Coveler, John B. Liao, Mark Burkard, Howard Bailey, KyungMann Kim, Thomas Havinghurst, Katina DeShong, Jennifer S. Childs, Eileen Dimond, Margaret Wojtowicz, Brandy M. Heckman-Stoddard, Denise Cecil, Mary Disis. Phase I trial of the safety and immunogenicity of a tri-antigen vaccine targeting HER2, IGFBP-2, and IGF-IR in patients with non-metastatic breast cancer [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 P2-02-02.

High-Risk Breast Lesions Diagnosed by Ultrasound-Guided Vacuum-Assisted Excision.

The aim of this study was to analyze the role of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of high-risk breast lesions and to evaluate the clinical and US features of the patients associated with recurrence or development of malignancy. Between April 2010 and September 2021, 73 lesions of 73 patients underwent US-guided VAE and were diagnosed with high-risk breast lesions. The incidence of recurrence or development of malignancy for high-risk breast lesions was evaluated at follow-up period. The clinical and US features of the patients were analyzed to identify the factors affecting the recurrence or development of malignancy rate. Only benign phyllodes tumors on US-guided VAE showed recurrences, while other high-risk breast lesions that were atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia/lobular carcinoma in situ), radial scar, and flat epithelial atypia did not show recurrences or malignant transformation. The recurrence rate of the benign phyllodes tumor was 20.8% (5/24) in a mean follow-up period of 34.3months. The recurrence rate of benign phyllodes tumor with distance from nipple of less than 1cm was significantly higher than that of lesions with distance from nipple of more than 1cm (75% vs. 10%, p < 0.05). Benign phyllodes tumors without concurrent breast cancer could be safely followed up instead of surgical excision after US-guided VAE when the lesions were classified as BI-RADS 3 or 4A by US.

Prediction of malignancy upgrade rate in high-risk breast lesions using an artificial intelligence model: a retrospective study

High-risk breast lesions (HRLs) are associated with future risk of breast cancer. Considering the pathological subtypes, malignancy upgrade rate differs according to each subtype and depends on various factors such as clinical and radiological features and biopsy method. Using artificial intelligence and machine learning models in breast imaging, evaluations can be made in terms of risk estimation in different research areas. This study aimed to develop a machine learning model to distinguish HRL cases requiring surgical excision from lesions with a low risk of accompanying malignancy. A total of 94 patients who were diagnosed with HRL by image-guided biopsy between January 2008 and March 2020 were included in the study. A structured database was created with clinical and radiological characteristics and histopathological results. A machine learning prediction model was created to make binary classifications of lesions as malignant or benign. Random forest, decision tree, K-nearest neighbors, logistic regression, support vector machine (SVM), and multilayer perceptron machine learning algorithms were used. Among these algorithms, SVM was the most successful. The estimations of malignancy for each case detected by artificial intelligence were combined and statistical analyses were performed. Considering all cases, the malignancy upgrade rate was 24.5%. A significant association was observed between malignancy upgrade rate and lesion size (P = 0.004), presence of mammography findings (P = 0.022), and breast imaging-reporting and data system category (P = 0.001). A statistically significant association was also found between the artificial intelligence prediction model and malignancy upgrade rate (P < 0.001). With the SVM model, an 84% accuracy and 0.786 area-underthe- curve score were obtained in classifying the data as benign or malignant. Our artificial intelligence model (SVM) can predict HRLs that can be followed up with a lower risk of accompanying malignancy. Unnecessary surgeries can be reduced, or second line vacuum excisions can be performed in HRLs, which are mostly benign, by evaluating on a case-by-case basis, in line with radiology-pathology compatibility and by using an artificial intelligence model.

Retrospective Cohort Study of Practical Applications of Paramagnetic Seed Localisation in Breast Carcinoma and Other Malignancies.

(1) Background: Paramagnetic seeds are a safe alternative for the wire-guided localisation of non-palpable breast lesions, but can also be applied for non-breast lesions. This study presents the experience with a paramagnetic seed, MagSeed® (Endomagnetics Ltd., Cambridge, UK, CE-registered and FDA-cleared), in an academic and non-academic breast centre. (2) Methods: Multicentre, retrospective analysis of 374 consecutive patients who underwent surgery after paramagnetic seed localisation (MSL) between 2018 and 2020. Indications for localisation included non-palpable breast lesions (n = 356), lymph nodes (n = 15) or soft tissue lesions (n = 3). The primary outcome was feasibility and the rate of positive section margins. The secondary outcome was predictive factors for positive section margins. (3) Results: The accurate excision of high-risk breast lesions, lymph nodes and soft tissue lesions was seen in 91.07% (n = 56). Positive section margins were observed in 7.86% (n = 25) after breast conserving surgery for invasive or ductal carcinoma in situ (DCIS) (n = 318). Invasive breast cancer associated with DCIS (p = 0.043) and the size of DCIS (p &lt; 0.001) were significantly correlated with the positive section margins. (4) Conclusion: This study confirms the feasibility of MSL, as well as the higher risk for positive margins in cases of breast carcinoma with associated DCIS. Soft tissue lesions and lymph nodes associated with other malignancies, e.g., melanoma, can also be localised with paramagnetic seeds. This offers perspectives for future applications, such as the de-escalation of axillary treatment in breast cancer.

78 (PB-078) Poster - The Impact on Management and Outcomes of Benign and High-Risk Breast Lesions After the Introduction of Vacuum Assisted Excision

Background: For benign lesions up to 3 cm, previous studies have shown that vacuum assisted excision (VAE) is a safe and effective alternative for surgical excision. However, the use of VAE for the management of high-risk lesions is controversial and guidelines are ambiguous. This study describes the impact of the implementation of VAE in terms of management and outcomes.