Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

A WNT4- and DKK3-driven canonical to noncanonical Wnt signaling switch controls multiciliogenesis.

Multiciliated cells contain hundreds of cilia whose directional movement powers the mucociliary clearance of the airways, a vital host defense mechanism. Multiciliated cell specification requires canonical Wnt signaling, which then must be turned off. Next, ciliogenesis and polarized ciliary orientation are regulated by noncanonical Wnt/planar cell polarity (Wnt/PCP) signaling. The mechanistic relationship between the Wnt pathways is unknown. We show that DKK3, a secreted canonical Wnt regulator and WNT4, a noncanonical Wnt ligand act together to facilitate a canonical to noncanonical Wnt signaling switch during multiciliated cell formation. In primary human airway epithelial cells, DKK3 and WNT4 CRISPR knockout blocks, whereas ectopic expression promotes, multiciliated cell formation by inhibiting canonical Wnt signaling. Wnt4 and Dkk3 single-knockout mice also display defective ciliated cells. DKK3 and WNT4 are co-secreted from basal stem cells and act directly on multiciliated cells via KREMEN1 and FZD6, respectively. We provide a novel mechanism that links specification to cilium biogenesis and polarization for proper multiciliated cell formation.

Targeting BET Proteins Decreases Hyaluronidase-1 in Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In this study, we evaluate the regulation of HYALs in PDAC. METHODS: Using siRNA and small molecule inhibitors, we evaluated the regulation of HYALs using quantitative real-time PCR (qRT-PCR), Western blot analysis, and ELISA. The binding of BRD2 protein on the HYAL1 promoter was evaluated by chromatin immunoprecipitation (ChIP) assay. Proliferation was evaluated by WST-1 assay. Mice with xenograft tumors were treated with BET inhibitors. The expression of HYALs in tumors was analyzed by immunohistochemistry and by qRT-PCR. RESULTS: We show that HYAL1, HYAL2, and HYAL3 are expressed in PDAC tumors and in PDAC and pancreatic stellate cell lines. We demonstrate that inhibitors targeting bromodomain and extra-terminal domain (BET) proteins, which are readers of histone acetylation marks, primarily decrease HYAL1 expression. We show that the BET family protein BRD2 regulates HYAL1 expression by binding to its promoter region and that HYAL1 downregulation decreases proliferation and enhances apoptosis of PDAC and stellate cell lines. Notably, BET inhibitors decrease the levels of HYAL1 expression in vivo without affecting the levels of HYAL2 or HYAL3. CONCLUSIONS: Our results demonstrate the pro-tumorigenic role of HYAL1 and identify the role of BRD2 in the regulation of HYAL1 in PDAC. Overall, these data enhance our understanding of the role and regulation of HYAL1 and provide the rationale for targeting HYAL1 in PDAC.

Robotic-Assisted Nipple Sparing Mastectomy.

Minimally invasive approaches to breast surgery have evolved from endoscopic techniques to recent developments in robotic-assisted mastectomies. Initial studies on robotic-assisted nipple-sparing mastectomy (RNSM) have shown improved patient satisfaction and aesthetic outcomes with similar complication rates and oncological outcomes in selected patients. This chapter reviews techniques used and available data on complications and clinical outcomes for RNSM. Currently, RNSM is an investigational technique in the United States and should be performed in clinical trials with U.S. Food & Drug Administration approval to rigorously evaluate the safety and effectiveness of this approach.

Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia.

Stress-adaptive mechanisms enable tumour cells to overcome metabolic constraints under nutrient and oxygen shortage. Aspartate is an endogenous metabolic limitation under hypoxic conditions, but the nature of the adaptive mechanisms that contribute to aspartate availability and hypoxic tumour growth are poorly understood. Here we identify GOT2-catalysed mitochondrial aspartate synthesis as an essential metabolic dependency for the proliferation of pancreatic tumour cells under hypoxic culture conditions. In contrast, GOT2-catalysed aspartate synthesis is dispensable for pancreatic tumour formation in vivo. The dependence of pancreatic tumour cells on aspartate synthesis is bypassed in part by a hypoxia-induced potentiation of extracellular protein scavenging via macropinocytosis. This effect is mutant KRAS dependent, and is mediated by hypoxia-inducible factor 1 (HIF1A) and its canonical target carbonic anhydrase-9 (CA9). Our findings reveal high plasticity of aspartate metabolism and define an adaptive regulatory role for macropinocytosis by which mutant KRAS tumours can overcome nutrient deprivation under hypoxic conditions.

Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker.

Exosomes are extracellular vesicles derived from the endosomal compartment that are potentially involved in intercellular communication. Here, we found that frequently used biomarkers of exosomes are heterogeneous, and do not exhibit universal utility across different cell types. To uncover ubiquitous and abundant proteins, we used an unbiased and quantitative proteomic approach based on super-stable isotope labeling with amino acids in cell culture (super-SILAC), coupled to high-resolution mass spectrometry. In total, 1,212 proteins were quantified in the proteome of exosomes, irrespective of the cellular source or isolation method. A cohort of 22 proteins was universally enriched. Fifteen proteins were consistently depleted in the proteome of exosomes compared to cells. Among the enriched proteins, we identified biogenesis-related proteins, GTPases and membrane proteins, such as CD47 and ITGB1. The cohort of depleted proteins in exosomes was predominantly composed of nuclear proteins. We identified syntenin-1 as a consistently abundant protein in exosomes from different cellular origins. Syntenin-1 is also present in exosomes across different species and biofluids, highlighting its potential use as a putative universal biomarker of exosomes. Our study provides a comprehensive quantitative atlas of core proteins ubiquitous to exosomes that can serve as a resource for the scientific community.

Relationship Between Financial Toxicity and Surgical Treatment for Early-Stage Breast Cancer: A Propensity Score-Matched Comparison of Breast-Conserving Therapy and Mastectomy.

BACKGROUND: Financial toxicity (FT) can lead to decreased quality of life and poor treatment outcomes. However, there is limited published data on the extent to which the various surgical treatment approaches for early-stage breast cancer are determinants for FT. STUDY DESIGN: We performed a single-institution cross-sectional survey of adult female patients with stage 0 to II breast cancer undergoing unilateral breast-conserving therapy or unilateral mastectomy. FT was measured using the Comprehensive Score for Financial Toxicity (COST) survey. Propensity matching was performed to optimize comparability of study groups. A multivariate regression model was used to identify factors associated with worsening FT as a robustness check. Our secondary end point was prevalence of coping strategies associated with cost of cancer care. RESULTS: Among 294 patients who met inclusion criteria, 203 underwent breast-conserving therapy and 91 received mastectomy. We generated 72 total matched pairs and noted no differences in demographic and socioeconomic characteristics. Of these, 55 pairs had complete COST information, which was comparable on adjusted analysis (26.6 vs 24.7; p = 0.481). High annual income (ß = 4.83; p < 0.001) and supplemental insurance (ß = 5.37; p < 0.001) were significantly associated with higher COST scores, while change in employment status (ß = -4.81; p < 0.001) correlated significantly with lower COST scores. No significant differences were observed in coping strategies. CONCLUSIONS: Choice of BCT or mastectomy was not associated with a differential risk for FT in early-stage cancer. Decisions on ablative approach should be made based on patient preferences and disease-specific criteria. Transparent counseling on FT for high-risk populations promotes patient-centricity.

Oncoplastic partial breast reconstruction: concepts and techniques.

Immediate oncoplastic breast reconstruction performed at the time of breast conserving surgery for the treatment of breast cancer merges the therapeutic goals of complete oncologic extirpation with preservation of breast form and function. A constellation of surgical techniques that employs breast volume displacement and/or replacement methods of varying complexity levels have emerged, thus broadening the potential applications for breast conservation therapy to include cases with increased tumor-to-native breast-volume ratios, multicentric or multifocal disease, and/or previous margin-positive resections. This review describes the various reconstructive methods, including the use of local tissue rearrangement, oncoplastic reduction-mastopexy, and locoregional flaps. Classification of the surgical options into levels I and II volume-displacement and volume-replacing techniques is made. Additionally, we explore the oncologic safety and effectiveness of this treatment paradigm by summarizing existing supportive evidence regarding associated risk of surgical complications, rate of margin-positive resection, implications for radiographic surveillance, local recurrence rates, and patient-reported outcomes. In conclusion, surgeons may use a wide variety of oncoplastic techniques for partial breast reconstruction at the time of segmental mastectomy to deliver effective breast conserving treatment for women with breast cancer. A growing body of literature affirms the oncologic safety of this approach. Future directions for research include long-term follow-up data with emphasis on outcomes from patient perspectives.

Autologous fat grafting in breast reconstruction: implications for follow-up and surveillance.

The procedural volume of autologous fat grafting (AFG) has risen over the past several years, specifically in the setting of breast reconstruction, despite controversy surrounding its oncologic safety. While some in vitro and animal models have cast doubt on the oncologic safety of AFG, there is no clinical evidence that AFG in breast reconstruction is associated with an increased risk of cancer development or recurrence or an inability to adequately assess changes in the breast. That being said, recommendations regarding surveillance and follow-up after AFG in breast reconstruction are largely surgeon directed and differ across practices. The purpose of this review is to summarize the current literature and provide evidence-based recommendations.

Correlation of circulating or disseminated tumor cells with the Oncotype DX Recurrence Score.

PURPOSE: New biomarkers are emerging to predict recurrence risk in women with early-stage breast cancer. High Oncotype DX Recurrence Score® (RS) is associated with worse disease-free and overall survival. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in breast cancer. We investigated the association between high RS and CTCs or DTCs. METHODS: Using a prospective database, we evaluated patients with hormone receptor-positive/HER2-negative, node-negative invasive breast cancer from 1/2005 to 1/2017. RS was classified using TAILORx study cutoff points: low (< 11), intermediate (11-25), and high (> 25). CTCs were assessed using CellSearch® and DTCs using cytospin specimens of bone marrow aspirates. Positive result was defined as one or more CTCs or DTCs identified. Chi-square analyses were utilized to evaluate the relationship between RS and CTCs or DTCs. RESULTS: 233 patients were identified from a prospective database, of which 96 had RS results. Of these patients, 88 had CTC results and 58 had DTC results. CTCs were detected in 17/88 (19%) patients, while DTCs were detected in 20/58 (34%). Patients with high RS were not more likely to have CTCs (18%) compared to patients with low/intermediate RS (20%; p = 0.919). Similarly, high RS was not associated with DTC detection, with DTCs present in 40% of patients with high RS versus 33% with low/intermediate RS (p = 0.687). In the subgroup of patients ≤ 50 years, no associations were found between high RS and CTCs (p = 0.383) or DTCs (p = 0.234). CONCLUSIONS: High Oncotype DX RS did not correlate with CTCs in blood or DTCs in bone marrow in our study.

Oncologic Safety and Surveillance of Autologous Fat Grafting following Breast Conservation Therapy.

BACKGROUND: Autologous fat grafting is a useful adjunct following breast reconstruction. The impact of autologous fat grafting on oncologic safety and surveillance remains questionable, particularly following breast conservation therapy. METHODS: The authors performed a retrospective review of patients who underwent delayed fat grafting following breast conservation therapy between 2006 and 2016. A control group of conservatively managed patients without grafting was matched for cancer stage, age, body mass index, and follow-up. Outcomes included locoregional recurrence and oncologic surveillance. RESULTS: Seventy-two patients were identified per cohort. There were no differences in median age (50 years versus 51 years; p = 0.87), body mass index (28.2 kg/m versus 27.2 kg/m; p = 0.38), or length of follow-up (61.9 months versus 66.8 months; p = 0.144) between controls and grafted patients, respectively. Overall, four patients in each cohort experienced recurrence (5.6 percent; p = 1.00) with similar cumulative incidence estimates observed (log-rank test, p = 0.534). There were no significant differences in palpable mass (9.7 percent versus 19.4 percent; p = 0.1), fat necrosis (34.7 percent versus 33.3 percent; p = 0.86), calcifications (37.5 percent versus 34.7 percent; p = 0.73), or indication for breast biopsy (15.3 percent versus 22.2 percent; p = 0.23) between breast conservation and breast conservation therapy plus autologous fat grafting cohorts, respectively. CONCLUSIONS: Overall, the authors found no difference in recurrence rates after breast conservation with or without delayed fat grafting. Furthermore, there were no differences in the rates of fat necrosis, palpable mass, and abnormal radiographic findings. This study represents the longest follow-up to date in in a large matched study of autologous fat grafting with breast conservation therapy demonstrating oncologic safety and no interference with follow-up surveillance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Outcomes of Volume Replacement Oncoplastic Breast-Conserving Surgery Using Chest Wall Perforator Flaps: Comparison with Volume Displacement Oncoplastic Surgery and Total Breast Reconstruction.

BACKGROUND: Volume replacement oncoplastic breast-conserving surgery (VR-OBCS) uses islanded or pedicled chest wall fasciocutaneous perforator flaps from outside of the breast footprint to replace the volume that has been excised during lumpectomy, extending the options for breast conservation to patients who may otherwise require mastectomy. This study compares outcomes for VR-OBCS with both standard volume displacement oncoplastic breast-conserving surgery (VD-OBCS) and mastectomy with immediate total breast reconstruction (TBR). METHODS: A retrospective cohort study was conducted; demographic data, clinicopathologic factors, surgical details, and postoperative events were collected until patients had completed their reconstructions. Variables were compared using the t test and analysis of variance test, or chi-square analysis and Fisher's exact test, as appropriate. RESULTS: Ninety-seven consecutive patients (109 immediate breast reconstruction procedures) were included: 43 percent underwent standard VD-OBCS procedures, 35 percent underwent mastectomy with immediate TBR, and VR-OBCS techniques were used in 22 percent, of which only one patient required a delayed procedure for symmetry. Mean whole tumor size was similar in the VR-OBCS and TBR groups and was significantly higher than for the VD-OBCS group (p < 0.05). Overall rate of complications affecting the breast area (p < 0.001), need for additional surgery to either breast (p < 0.001), and time to reconstruction completion (p < 0.001) were significantly higher in the TBR group. CONCLUSIONS: VR-OBCS extends the options for breast conservation to many patients that would otherwise require mastectomy. The complication rate is lower, fewer procedures are necessary, and less time is required to complete the reconstruction when compared with mastectomy and immediate TBR. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Activin A Modulates Inflammation in Acute Pancreatitis and Strongly Predicts Severe Disease Independent of Body Mass Index.

INTRODUCTION: Acute pancreatitis (AP) is a healthcare challenge with considerable mortality. Treatment is limited to supportive care, highlighting the need to investigate disease drivers and prognostic markers. Activin A is an established mediator of inflammatory responses, and its serum levels correlate with AP severity. We hypothesized that activin A is independent of body mass index (BMI) and is a targetable promoter of the AP inflammatory response. METHODS: We assessed whether BMI and serum activin A levels are independent markers to determine disease severity in a cohort of patients with AP. To evaluate activin A inhibition as a therapeutic, we used a cerulein-induced murine model of AP and treated mice with activin A-specific neutralizing antibody or immunoglobulin G control, both before and during the development of AP. We measured the production and release of activin A by pancreas and macrophage cell lines and observed the activation of macrophages after activin A treatment. RESULTS: BMI and activin A independently predicted severe AP in patients. Inhibiting activin A in AP mice reduced disease severity and local immune cell infiltration. Inflammatory stimulation led to activin A production and release by pancreas cells but not by macrophages. Macrophages were activated by activin A, suggesting activin A might promote inflammation in the pancreas in response to injury. DISCUSSION: Activin A provides a promising therapeutic target to interrupt the cycle of inflammation and tissue damage in AP progression. Moreover, assessing activin A and BMI in patients on hospital admission could provide important predictive measures for screening patients likely to develop severe disease.

Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6-12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term gemcitabine administration on the tumor microenvironment to identify potential therapeutic options for chemorefractory PDAC. Using a combination of mouse models, primary cell line-derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFß-associated signals. These secreted factors altered the composition of the tumor stroma, conferring gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFß1 biosynthesis. Combined gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFß signaling. In the setting of TGFß signaling deficiency, gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of gemcitabine-refractory PDAC. SIGNIFICANCE: These data suggest that long-term treatment with gemcitabine leads to extensive reprogramming of the pancreatic tumor microenvironment and that patients who progress on gemcitabine-based regimens may benefit from multidrug immunotherapy.See related commentary by Carpenter et al., p. 3070 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/15/3101/F1.large.jpg.

Effectiveness and Safety of Magseed-localization for Excision of Breast Lesions: A Prospective, Phase IV Trial.

OBJECTIVE: A prospective, phase IV study was conducted to assess the effectiveness of Magseed to localize breast lesions requiring surgical excision. BACKGROUND: Since FDA approval in 2016, Magseed has been increasingly used to localize non-palpable lesions due to advantages over wires or radioactive seeds. This is the first prospective, post marketing trial of Magseed. METHODS: From 1/2017-2/2018, 107 women with lesions requiring localization were enrolled at a single institution. Primary endpoint was Magseed retrieval rate. Secondary endpoints were adverse events, accuracy of placement, surgery duration and positive margin rate. Clinicians were surveyed for ease of use using a Likert scale. Descriptive statistics and Fisher's exact test were performed to assess univariable associations with positive margins. RESULTS: There were 124 Magseeds placed including one marker in 93 subjects, 2 markers in 11 and 3 markers in 3. The majority of lesions were masses (63%) followed by calcifications (24%). All 124 Magseeds were placed within 10mm of the target lesion and surgically retrieved with median operative time of 15min (range 4-47). No device-related adverse events occurred. Of the 98 malignant lesions, 9 had positive margins and 7 of them underwent a second surgery for additional margins. On univariable analysis, age ≤ 50 (25.0% vs 6.4%, p=0.04), lesion histology (p = 0.03), and pathologic T-stage (p = 0.04) were significantly associated with positive margins. Clinicians rated the Magseed very or fairly easy to use in most cases. CONCLUSIONS: The Magseed system for localization of non-palpable lesions was effective and safe; all markers were successfully retrieved with margin-negative resections in 91%. This study supports use of Magseed for localization of breast lesions.