Sentinel Lymph Nodes In Breast Cancer Research Articles

ThP1.2 - Management of breast cancer sentinel lymph node macrometastasis in the axilla; audit of current unit practice and evaluation of factors that influence patient management

Abstract Aims Detection of sentinel lymph node (SLN) macrometastasis for breast cancer no longer mandates further axillary surgery. Association of Breast Surgery (ABS) guideline provides recommendation to optimise patient management. It also acknowledges management uncertainties in specific patient groups. We aimed to examine our unit practice against national guideline and evaluate potential factors that influence axillary management. Methods Retrospective analysis of prospectively maintained electronic database determined clinico-pathological characteristics on patients diagnosed with SLN macrometastasis (n=127) at the Leeds Breast Unit (2020-2022). Axillary management was compared against ABS guideline. Results 56 (44.1%) received completion axillary node clearance (cANC), 37 (29.1%) axillary radiotherapy (aRT), and 34 (26.8%) no further axillary treatment. 80.3% had one macrometastasis. As per guideline, all patients who had >3 macrometastasis (n=10) underwent cANC. Type of breast surgery (mastectomy vs. breast conserving surgery; BCS) did not affect further axillary treatment rate (76.7% vs. 70.1%). Type of further axillary treatment varied with cANC commonest for mastectomy patients (78.3%) and aRT commonest for BCS patients (57.4%). In contrast to the guideline, 58% of post-menopausal BCS patients with ER+HER2- T1 tumours (n=12) received further axillary treatment. Where guideline stated management uncertainty, further axillary treatment was frequent; pre-menopausal patients (82%), T2 tumours (73%), lymphovascular invasion (74%), and extranodal spread (77%). Conclusion Our unit’s SLN macrometastasis management is mostly in line with national guideline but further work is required to avoid overtreatment. Where management uncertainty exists, patients commonly received further axillary treatment. Further research is required in these patient groups to optimise axillary management.

Value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of SLN in breast cancer

BACKGROUND: Accurate sentinel lymph node (SLN) characterization is essential for breast cancer management, prompting advancements in imaging technologies such as contrast-enhanced ultrasound (CEUS) and sound touch quantification (STQ) to enhance diagnostic precision. OBJECTIVE: To explore the value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of sentinel lymph node (SLN) in breast cancer. METHODS: A total of 91 breast cancer patients (91 SLNs) admitted to the hospital from February 2022 to December 2023 were selected for this study. Among them, 26 patients with metastatic SLN confirmed by surgery and pathology were included in the metastatic SLN group, and 65 patients with non-metastatic SLN were included in the non-metastatic SLN group. Preoperative examination results of CEUS and STQ were retrospectively analyzed. The diagnostic efficacy of perfusion characteristics evaluated by CEUS and STQ parameters for the properties of SLN in breast cancer was analyzed using the receiver operating characteristics (ROC) curve. Statistical methods such as chi-square tests and logistic regression analysis were employed to analyze the data. RESULTS: Enhancement patterns differed significantly between the metastatic SLN and non-metastatic SLN groups (p< 0.05). ROC curve analysis indicated that CEUS perfusion characteristics had an AUC value of 0.823 for diagnosing SLN properties, with a sensitivity of 84.62% and specificity of 70.77% using type I as the critical value. Additionally, STQ measurement showed significantly higher values in the metastatic SLN group (44.18 ± 6.53 kPa) compared to the non-metastatic SLN group (34.69 ± 6.81 kPa) (t= 6.075, p< 0.001). The AUC value for STQ parameters in diagnosing metastatic SLN was 0.849, with a sensitivity of 73.08% and specificity of 92.31% using 42.40 kPa as the critical value. Though the AUC value of STQ measurement was higher than CEUS perfusion characteristics alone, the difference was not statistically significant (Z= 0.393, p= 0.695). Moreover, combining CEUS perfusion characteristics with STQ parameters yielded an AUC value of 0.815 for diagnosing SLN properties, showing no significant difference compared to diagnosis with CEUS or STQ parameters alone (Z= 0.149, 0.516, p= 0.882, 0.606). CONCLUSION: Combined use of perfusion characteristics evaluated by CEUS and STQ parameters can significantly improve the diagnostic specificity of SLN in breast cancer. It is worthy of clinical promotion.

Abstract PO4-07-10: Validation of An Ultrasound-Based Scoring System of Axillary Metastasis in Breast Cancer

Abstract Introduction: Ultrasound is the imaging modality of choice in the evaluation of axillary involvement in breast cancer. Our group previously created a scoring method to predict axillary lymph node metastasis (ALNM) based on ultrasound characteristics. In this study we validated the model and tested it among different Memorial Sloan Kettering Breast Cancer Sentinel Lymph Node Metastasis Nomogram1 (MSK) subgroups. Methods: The ultrasound score (table 1) was previously developed using data collected at a single institution from 2019 – 2021 by allocating points based on the regression coefficients of variables found to significantly predict ALNM. Subsequent evaluation of the discrimination of this model found it was robust to different patient demographic and tumor characteristics based on receiver operating characteristic curve analysis2. In this study, we validated the test statistics of our score at an outside institution. We also pooled patients from both institutions and evaluated the score performance in different MSK subgroups by the likelihood for sentinel node metastasis based off of clinical and pathologic data without accounting for imaging findings. Results: Between 2019-2021, 140 patients with breast cancer were analyzed for validation of the axillary ultrasound scoring system and when combined with the dataset of patients from the index institution, 358 pooled patients were stratified by predicted ALNM positivity according to MSK. In the validation cohort, the NPV for low risk (0-1) scores was 87%, while the PPV for high-risk (5+) scores was 71%. Overall in the combined cohort, 241 (67%) patients had low risk (0-1) axillary ultrasound scores and 33 (9%) had high risk (5+) scores. In this combined cohort, NPV was 84% (203/241 low-risk score patients were node negative), while PPV for high-risk scores was 85% (28/33 high risk score patients were node positive). When analyzed according to level of MSK predicted ALNM rates, for patients with < 50% predicted ALNM positivity, the NPV of low-risk scores was 87-89% and the PPV for high-risk axillary scores was 100%. For patients with >50% predicted ALNM positivity, the NPV of low-risk scores was 66% and the PPV of high-risk scores was 82%. Conclusions: A scoring system to predict ALNM among biopsy proven breast cancer patients undergoing upfront surgery was successfully developed from a multivariate model based on axillary ultrasound characteristics. This model was validated at a separate institution. The scoring system shows advantageous negative and positive predictive values for axillary node metastasis, especially among patients with < 50% predicted nodal involvement based on the MSK nomogram. This data may help foster better communication about ALNM risk between radiologists and treating clinicians to inform treatment decisions. Table. Scoring System for Likelihood of ALNM based on Ultrasound Characteristics Citation Format: Spencer Van Decar, Elizabeth Carpenter, Alexandra Adams, Jason Shore, Iulian Dragusin, Erika Davis, Craig Tork, Robert Krell, Troy Graybeal, Katherine Clifton, Arianna Buckley, Guy Clifton. Validation of An Ultrasound-Based Scoring System of Axillary Metastasis in Breast Cancer [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 PO4-07-10.

Sentinel node in breast cancer as an indicator of quality in medical care: Evaluation of statistics in Colombia.

Sentinel lymph node biopsy in breast cancer is considered the standard of staging in cases of clinically negative lymph nodes. Its omission in favor of axillary dissection generates significant morbidity. To determine the total number of sentinel node biopsy procedures in breast cancer in Colombia from 2017 through 2020, model and analyze them as if they were performed only in stage I breast cancer patients, and integrate their results into the concepts of quality of medical care. Search in a database of the Ministry of Health and Social Protection of Colombia with sentinel lymph node biopsy codes, and filters of breast cancer and year. Their results are contrasted with the number of cases in stage I of breast cancer. Breast cancer TNM staging was reported in 22154 cases, 3648 stage I. In the same time frame, the number of sentinel lymph node biopsies for breast cancer in Colombia was 1045, 28.64% of the total cases reported in stage I. Colombia is far from complying with the standard indicator of sentinel lymph node biopsy. It is recommended to concentrate breast cancer cases in hospitals that provide the conditions for its performance.

A Four-Arm Randomized Clinical Trial of Topical Pain Control for Sentinel Node Radiotracer Injections in Patients with Breast Cancer.

Radioactive tracer injections for breast cancer sentinel lymph node mapping can be painful. In this randomized trial, we compared four approaches to topical pain control for radiotracer injections. Breast cancer patients were randomized (9 April 2021-8 May 2022) to receive the institutional standard of ice prior to injection (n=44), or one of three treatments: ice plus a vibrating distraction device (Buzzy®; n=39), 4% lidocaine patch (n=44), or 4% lidocaine patch plus ice plus Buzzy® (n=40). Patients completed the Wong-Baker FACES® pain score (primary outcome) and a satisfaction with pain control received scale (secondary). Nuclear medicine technologists (n=8) rated perceived pain control and ease of administration for each patient. At study conclusion, technologists rank-ordered treatments. Data were analyzed as intention-to-treat. Wilcoxon rank-sum tests were used to compare pain scores of control versus pooled treatment arms (primary) and then control to each treatment arm individually (secondary). There were no differences in pain scores between the control and treatment groups, both pooled and individually. Eighty-five percent of patients were 'satisfied/very satisfied' with treatment received, with no differences between groups. No differences in providers' perceptions of pain were observed, although providers perceived treatments involving Buzzy© more difficult to administer (p<0.001). Providers rated lidocaine patch as the easiest, with ice being second. In this randomized trial, no differences in patient-reported pain or satisfaction with treatment was observed between ice and other topical treatments. Providers found treatments using Buzzy® more difficult to administer. Given patient satisfaction and ease of administration, ice is a reasonable standard.

Multimodal ultrasound imaging: a method to improve the accuracy of sentinel lymph node diagnosis in breast cancer.

This study assessed the utility of multimodal ultrasound in enhancing the accuracy of breast cancer sentinel lymph node (SLN) assessment and compared it with single-modality ultrasound. Preoperative examinations, including two-dimensional ultrasound (2D US), intradermal contrast-enhanced ultrasound (CEUS), intravenous CEUS, shear-wave elastography (SWE), and surface localization, were conducted on 86 SLNs from breast cancer patients. The diagnostic performance of single and multimodal approaches for detecting metastatic SLNs was compared to postoperative pathological results. Among the 86 SLNs, 29 were pathologically diagnosed as metastatic, and 57 as non-metastatic. Single-modality ultrasounds had AUC values of 0.826 (intradermal CEUS), 0.705 (intravenous CEUS), 0.678 (2D US), and 0.677 (SWE), respectively. Intradermal CEUS significantly outperformed the other methods (p<0.05), while the remaining three methods had no statistically significant differences (p>0.05). Multimodal ultrasound, combining intradermal CEUS, intravenous CEUS, 2D US, and SWE, achieved an AUC of 0.893, with 86.21% sensitivity and 84.21% specificity. The DeLong test confirmed that multimodal ultrasound was significantly better than the four single-modal ultrasound methods (p<0.05). Decision curve analysis and clinical impact curves demonstrated the superior performance of multimodal ultrasound in identifying high-risk SLN patients. Multimodal ultrasound improves breast cancer SLN identification and diagnostic accuracy.

The value of the improved percutaneous and intravenous contrast-enhanced ultrasound diagnostic classification in sentinel lymph nodes of breast cancer.

Metastatic burden of sentinel lymph node (SLN) in breast cancer patient is the basis for the decision to choose SLN biopsy or axillary lymph node dissection (ALND). However, the diagnostic performance of the previous percutaneous contrast-enhanced ultrasound (P-CEUS) and intravenous contrast-enhanced ultrasound (IV-CEUS) pattern were not satisfied. This study aimed to establish new classification based on structural characteristics for P-CEUS and IV-CEUS of SLN in breast cancer and evaluate the diagnostic efficacy. This retrospective study included consecutive breast cancer patients who had not received neoadjuvant therapy in the First Affiliated Hospital of Sun Yat-sen University between June 2019 and December 2021. Conventional ultrasound, P-CEUS and IV-CEUS were performed. The new classification methods for P-CEUS and IV-CEUS of SLN were established based on structural characteristics of SLN. Pathology was considered as the gold standard, the diagnostic efficacy of P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound in SLNs was analyzed. The detection rate of SLN by P-CEUS in 368 patients was 95.42%. The P-CEUS pattern of SLNs was divided into six types. The IV-CEUS sequence was divided into three types. The IV-CEUS mode was divided into four types. Among the 438 SLNs detected by P-CEUS, 105 (23.97%) were malignant and 333 (76.03%) were benign. Among the previously classified P-CEUS, P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound, the latter had the highest diagnostic efficacy (P<0.05), with sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under curve (AUC) of 81.90% (86/105), 97.30% (324/333), 90.53% (86/95), 94.46% (324/343), 93.61% (410/438) and 0.896 (0.864-0.923), respectively. The new classification of the P-CEUS and IV-CEUS features of SLNs was performed based on structural characteristics of lymph nodes. Compared with the previously classified P-CEUS, the new classification method has higher diagnostic performance. The combination of new classified P-CEUS and IV-CEUS is helpful to further improve the diagnostic performance of SLNs.

Pharmacoeconomic study of fluorescent lymphography and radionuclide diagnostics methods for sentinel lymph node detection in breast cancer

Background. Sentinel lymph node (SLN) biopsy is a reliable diagnostic method used to assess the spread of the malignant process in regional lymph nodes. Currently, this method is of great importance in treatment planning for early breast cancer and allows to avoid immediate and long-term complications of lymph node dissection. SLN detection can be performed using the radionuclide method, the disadvantages of which are associated with the peculiarities of working with radiopharmaceuticals and additional costs when using them. An alternative method is fluorescence lymphography (FL) with indocyanine green.Objective: performing a pharmacoeconomical study (cost-effectiveness analysis) comparing the cost-effectiveness of methods for detecting SLN in breast cancer: radionuclide diagnosis (RD) using a radiopharmaceutical based on sodium pertechnetate [99mТс] and FL using indocyanine green (Life Sciences OCPK LLC, Russia) and "IC GOR System" device (Central Design Bureau of Information and Control Systems JSC, Russia).Material and methods. The values of the cost-effectiveness ratio (CER) were calculated and compared for the two indicated methods of detecting SLN in breast cancer. Information on the RD method clinical efficacy was taken from the published data. SLN detection by the FL method with the use of indocyanine green and domestic apparatus was performed on the basis of the Regional Clinical Oncology Dispensary (Ryazan) in 53 patients with breast cancer. To assess the reliability of the obtained results a deterministic multivariate sensitivity analysis was performed.Results. The obtained CERFL values were significantly lower than the median CERRD values by average of 43.29% (p&lt;0.001): from 40.36% (p&lt;0.001) to 44.96% (p&lt;0.001). The geometric mean CERFL was lower than CERRD by 39,40% (from 37.99% to 42.80%), and their 95% confidence intervals (CI) did not intersect. Deterministic multivariate sensitivity analysis demonstrated robustness of the obtained data to the transformation of RD cost parameters. Nevertheless the geometric mean and its 95% CI of CERRD and CERFL did not intersect under any circumstances.Conclusion. According to the results of a pharmacoeconomic study, it is more economically profitable to detect SLN in breast cancer using indocyanine green and a domestic device for FL, as its costs per unit of efficiency were 38–45% lower than for RD using a radiopharmaceutical based on sodium pertechnetate [99mТс].

Magnetic Seed vs Guidewire Breast Cancer Localization With Magnetic Lymph Node Detection

Guidewires have been the standard for breast lesion localization but pose operative and logistic challenges. Paramagnetic seeds have shown promising results, but to the authors' knowledge, no randomized comparison has been performed. To determine whether the combination of a paramagnetic seed and superparamagnetic iron oxide (SPIO) is equivalent to guidewire and SPIO for breast cancer localization and sentinel lymph node detection (SLND). This was a phase 3, pragmatic, equivalence, 2-arm, open-label, randomized clinical trial conducted at 3 university and/or community hospitals in Sweden from May 2018 to May 2022. Included in the study were patients with early breast cancer planned for breast conservation and SLND. Study data were analyzed July to November 2022. Participants were randomly assigned 1:1 to a paramagnetic seed or a guidewire. All patients underwent SLND with SPIO. Re-excision rate and resection ratio (defined as actual resection volume / optimal resection volume). A total of 426 women (median [IQR] age, 65 [56-71] years; median [IQR] tumor size, 11 [8-15] mm) were included in the study. The re-excision rate was 2.90% (95% CI, 1.60%-4.80%), and the median (IQR) resection ratio was 1.96 (1.15-3.44). No differences were found between the guidewire and the seed in re-excisions (6 of 211 [2.84%] vs 6 of 209 [2.87%]; difference, -0.03%; 95% CI, -3.20% to 3.20%; P = .99) or resection ratio (median, 1.93; IQR, 1.18-3.43 vs median, 2.01; IQR, 1.11-3.47; P = .70). Overall SLN detection was 98.6% (95% CI, 97.1%-99.4%) with no differences between arms (203 of 207 [98.1%] vs 204 of 206 [99.0%]; difference, -0.9%; 95% CI, -3.6% to 1.8%; P = .72). More failed localizations occurred with the guidewire (21 of 208 [10.1%] vs 4 of 215 [1.9%]; difference, 8.2%; 95% CI, 3.3%-13.2%; P < .001). Median (IQR) time to specimen excision was shorter for the seed (15 [10-22] minutes vs 18 [12-30] minutes; P = .01), as was the total operative time (69 [56-86] minutes vs 75.5 [59-101] minutes; P = .03). The experience of surgeons, radiologists, and surgical coordinators was better with the seed. The combination of SPIO and a paramagnetic seed performed comparably with SPIO and guidewire for breast cancer conserving surgery and resulted in more successful localizations, shorter operative times, and better experience. ISRCTN.org Identifier: ISRCTN11914537.

Clinical use of Indocyanine green fluorescence method for sentinel lymph node biopsy in breast cancer in France in 2021

IntroductionIndocyanine green (ICG) for axillary sentinel lymph node (SLN) detection in early breast cancer is at least equivalent to radioisotopic and/or colorimetric techniques. This procedure has not yet been recommended by learned societies in France. Following the recent drug approval of Infracyanin ® in this indication, we wished to study the use of ICG in France. MethodsWe conducted a web-based survey among members of multiple French breast cancer societies throughout November 2021. The survey assessed the profile of the respondent, the use or not of ICG for the detection of SLN in breast cancer, the technique used and the opinion of non-users and their expectations on the subject. ResultsSeventy-five surgeons participated. More than a third (37 %) have been using ICG for the detection of SLN in breast cancer for 2 to 3 years. Technique was highly variable. According to 82.1 % of the respondents, less than 20 procedures are necessary to master the use of ICG. The main advantage reported for this method is the reduction of organizational constraints. The obstacles to the use of the ICG are the near infra-red camera equipment, but also the lack of validation by the French guidelines. Among non-users, 83 % would like to develop this technique in their center and 72.3 % are interested in training on this subject. ConclusionThis work highlights the need for French learned societies to take a stand on this issue but also the need to carry out studies on the technical aspects in order to standardise practices.

Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

The prognostic value of the histological shape of tumor negative sentinel nodes in breast cancer.

Sentinel lymph node (SLN) metastasis is an important predictor of prognosis in breast cancer (BC) patients, guiding treatment decisions. However, patients with the same BC subtype and tumor negative SLN (SLNneg) can have different survival outcomes. We hypothesized that the host anti-tumor immune reaction in SLNneg is important and results in morphometrically measurable changes in SLN size or shape which are related to patient prognosis. Surface area, circumference, long axis and short axis were histologically measured in 694 SLNneg from 356 cases of invasive BC and 67 ductal carcinoma in situ cases. The area occupied by fat was categorized as less or more than 50%. The long to short axis (L/S) ratio was calculated. The relationship between SLNneg morphometries and clinicopathological variables like tumor-infiltrating lymphocytes (TILs) within the primary tumor, as well as prognosis at 10 years follow up were analyzed. The mean SLNneg surface area was 78.7mm2, circumference 40.3mm, long axis 13.1mm, short axis 8.2mm and L/S ratio 1.7. Larger surface area, long axis and short axis, including age >55 years were associated with higher body mass index (BMI) and SLN fat over 50% (p<0.003). In invasive BC, a high SLNneg L/S ratio (≥1.9) was related to poorer disease-free (HR=1.805, 95%CI 1.182-2.755, p=0.006) and overall (HR=2.389, 95%CI 1.481-3.851, p<0.001) survival. A low SLNneg L/S ratio (<1.9) was associated with high TILs in the primary BC (≥10%) (p=0.005). However a high TIL count was not of prognostic relevance. This is the first study to suggest that morphometric characteristics of axillary SLNneg, like L/S ratio, could be used to predict prognosis in patients with SLNneg invasive BC of all subtypes. The association between low L/S ratio and high TILs suggest that SLN shape is related to immunological functioning of the SLN and could be used in addition to TIL evaluation. Regarding the dubious role of TILs in hormone receptor positive breast cancer, SLNneg morphometry to gain information about host immune status could especially be of benefit in this subtype. Further studies are warranted to better understand the underlying biological mechanisms.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images

BackgroundSentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images. MethodsUsing a ResNet 50 architecture pretrained on ImageNet and a previously successful strategy, we trained deep learning (DL)-based image analysis algorithms to predict sentinel status on hematoxylin/eosin-stained images of predominantly luminal, primary breast tumours from the INSEMA trial and three additional, independent cohorts (The Cancer Genome Atlas (TCGA) and cohorts from the University hospitals of Mannheim and Regensburg), and compared their performance with that of a logistic regression using clinical data only. Performance on an INSEMA hold-out set was investigated in a blinded manner. ResultsNone of the generated image analysis algorithms yielded significantly better than random areas under the receiver operating characteristic curves on the test sets, including the hold-out test set from INSEMA. In contrast, the logistic regression fitted on the Mannheim cohort retained a better than random performance on INSEMA and Regensburg. Including the image analysis model output in the logistic regression did not improve performance further on INSEMA. ConclusionsEmploying DL-based image analysis on histological slides, we could not predict SLN status for unseen cases in the INSEMA trial and other predominantly luminal cohorts.

ASO Visual Abstract: A Novel Injection Protocol Using Voluven®-Assisted Indocyanine Green with Improved Near-Infrared Fluorescence Guidance in Breast Cancer Sentinel Lymph Node Mapping: A Translational Study.

ASO Visual Abstract: A Novel Injection Protocol Using Voluven®-Assisted Indocyanine Green with Improved Near-Infrared Fluorescence Guidance in Breast Cancer Sentinel Lymph Node Mapping: A Translational Study.

A Novel Injection Protocol Using Voluven®-Assisted Indocyanine Green with Improved Near-Infrared Fluorescence Guidance in Breast Cancer Sentinel Lymph Node Mapping—A Translational Study

BackgroundNear-infrared (NIR) fluorescence-guided surgery with indocyanine green (ICG) has been demonstrated to provide high sensitivity in sentinel lymph node biopsy (SLNB) for breast cancer but has several limitations, such as unstable pharmacokinetics, limited fluorescence brightness, and undesired diffusion to neighboring tissues. This paper investigates the use of Voluven® as the solvent for ICG fluorescence-guided SLNB (ICG-SLNB).MethodsThe photophysical properties of ICG in water and Voluven® were evaluated in laboratory experiments and in a mouse model. Nine patients with early breast cancer underwent subareolar injection of diluted ICG (0.25 mg/ml) for ICG-SLNB. Six of the nine patients received ICG dissolved in Voluven® (ICG:Voluven®), while three were administered ICG dissolved in water (ICG:water); a repetitive injection-observation protocol was followed for all patients. The mapping image quality was evaluated.ResultsLaboratory experiments and in vivo mouse study showed improved fluorescence and better targeting using Voluven® as the solvent. ICG-SLNB with a repetitive injection-observation protocol was successfully performed in all nine patients. ICG:Voluven® administration had an overall better signal-to-background ratio (SBR) in sequential sentinel lymph nodes. The rates of transportation within the lymphatics were also improved using ICG:Voluven® compared with ICG:water.ConclusionsFrom basic research to animal models to in-human trial, our study proposes a repetitive injection-observation technique with ICG:Voluven®, which is characterized by better transportation and more stable mapping quality for ICG-SLNB in breast cancer patients.

Can inflammatory indices predict sentinel lymph node status in patients with early-stage breast cancer?

Breast cancer research has focused on the early detection and treatment of breast cancer. Axillary lymph node status is essential for primary breast cancer staging, recurrence, and survival. The current quest for precision medicine is to identify predictive markers that offer the advantage of individualized treatment options. This study aimed to investigate the value of inflammatory indices in predicting positive sentinel nodes in breast cancer. We studied 602 patients with early-stage breast cancer who underwent sentinel lymph node biopsies (SLNB) at the Bülent Ecevit University General Surgery Clinic. We obtained data, including the clinical and demographic characteristics of the patients, such as age, histological type, and sentinel lymph nodes. Neutrophil, lymphocyte, platelet, and monocyte counts were obtained from preoperative complete blood count test data from the patient registry. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory index (SII), and sentinel lymph node biopsy were analyzed. Sentinel LAP was negative in 391 (65%) patients and positive in 211 (35%). In the receiver operating characteristic curve analysis, no significant difference was found between SLNB positivity and negativity in terms of NLR, PLR, LMR, or SII. In contrast to previous research, NLR, PLR, LMR, or SII did not affect SLNB positivity prediction in our study.

Gene expression comparison between primary aggressive luminal breast cancer and paired axillary and sentinel lymph node metastasis.

e13060 Background: More aggressive and therapy-resistant hormone receptor (HR)-positive breast cancer (hereafter luminal breast cancer, LBC) remains a great challenge. Few studies examine the genomics of axillary lymph node (ALN) metastasis in LBC. The aim of this study was to characterize and compare the mRNA expression patterns of primary breast cancers and paired ALN metastases. Methods: Aggressive pT1-2N2-3M0 LBC patients aged over 18 years who were treated at Shandong Provincial Hospital Affiliated to Shandong First Medical University and had available matched primary and metastatic tumor samples for gene expression analyses were retrospectively recruited. Bulk mRNA expression levels were determined by RNA sequencing (Illumina NovaSeq 6000 system) and calculated using featureCounts. Differential gene expression analysis was performed using DESeq2. All analyses were carried out with differentially expressed genes (DEGs) with an FDR &lt;0.05. Changes of intrinsic subtypes from primary to metastatic disease were assessed. Results: Ten LBC patients with paired tumor samples were included. Compared with the primary tumor, ALN metastatic tumor had 1509 statistically significant DEGs, including 743 upregulated genes and 766 downregulated genes. Notably, there was an upregulation of genes related to immune response-activating signal transduction, T cell receptor signaling pathway, B cell receptor signaling pathway, and cytokine-cytokine receptor interaction in the ALN metastasis. The downregulation of genes were mainly enriched in the PI3K-Akt signaling pathway, ECM-receptor interaction, Wnt signaling pathway, and TGF-beta signaling pathway. Intrinsic subtype distribution in primary tumors was different from those in ALN metastatic tumors, such as Luminal A (30% vs. 50%), Luminal B (10% vs. 20%), HER2-enriched (20% vs. 10%), Basal-like (10% vs. 10%), and Normal-like (30% vs. 10%). These results suggest that LBC is a highly heterogeneous disease. Conclusions: In aggressive pT1-2N2-3M0 LBC, ALN metastases have a distinct gene expression profile and show upregulation of immune-related genes ( CR2, BLK, PAX5, CD19, FCRL1, TNFRSF13B). Genes associated with signaling pathways are involved in the development of breast cancer ( FST, TNN, LAMC3, SFRP2, FGF18), and are downregulated when compared to autologous primary cancer. These pathways are potential targeted pathways in the treatment of breast cancer. LBC cells metastatic to lymph nodes undergo a change to metastasize and survive in the new microenvironment, which may provide insights into the metastatic process. Besides, a switch towards more aggressive intrinsic subtype from primary to advanced disease is also observed.

Level I axillary dissection in patients with breast cancer and tumor-involved sentinel lymph node after NAC is not sufficient for adequate nodal staging.

The purpose of the study was to investigate the oncological sufficiency of level I axillary dissection for adequate histological nodal staging (ypN) in patients with breast cancer and tumor-involved sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC). A prospective multicentre pilot study took place from 01.01.2018 to 30.11.2020 in three mammary centres in the Czech Republic in patients with breast cancer after NAC (NCT03556397). Patients in the cohort with positive histological frozen section of SLN were indicated to separate axillary dissection of levels I and II. Sixty-one patients with breast cancer after NAC were included in the study according to inclusion and exclusion criteria. Twelve patients with breast cancer and tumour involved SLN after NAC were further included in the analysis. Two (16.7%) patients had positive non-sentinel lymph nodes in level I only, one (8.3%) patient had positive lymph nodes in level II only, and seven (58.3%) patients had positive lymph nodes in both levels. Level I axillary dissection in a patient with tumour involved SLN after NAC would have resulted in understaging in five (41.7%) patients, mostly ypN1 instead of ypN2. According to our pilot result, level I axillary dissection is not sufficient in terms of adequate histological nodal staging in breast cancer patients after NAC, and level II axillary dissection should not be omitted.

Abstract P1-10-17: Axillary radiotherapy in selected patients with a preoperative diagnosis of lymph node involvement is a safe alternative to axillary lymph node dissection

Abstract Introduction: Axillary lymph node dissection (ALND) is associated with significant morbidity. Randomised data [1,2] suggest that axillary radiotherapy (RT), or no further axillary treatment beyond sentinel node biopsy (SNB) may be safe. There are very few studies to guide the management of preoperatively diagnosed lymph node metastases either in the context of neoadjuvant chemotherapy (NACT) or direct to surgery. The current UK recommendation is for ALND. In 2015 our policy changed to RT for carefully selected patients after MDT discussion. These data look at axillary recurrence for those patients having axillary RT Methods: Data were retrospectively collected on patients with preoperatively diagnosed lymph node metastases between January 2016 and December 2020. Patients undergoing surgery with a curative intent were included. The decision to offer axillary RT was made in the MDT based on clinical and radiological findings and the burden of disease in the axillary sample. Axillary recurrence was defined as disease recurring in the axilla with no distant disease. Results: Date were collected on 132 patients. Demographics and tumour status are outlined in Table 1. 55% of patients had neoadjuvant chemotherapy with a 52% path CR in the axilla. Table 2 gives the results for the axillary RT group. During the same time period 25 patient had ALND. Of those 2 (8%) had isolated LN recurrence. 18 patients had axillary RT following positive SLN after NACT. There was a single patient with axillary recurrence in this group. Conclusion: In the absence of randomised data to guide practice, these data show that in selected patients axillary radiotherapy is safe after axillary node sampling. The decision should be based on axillary burden, tumour biology, MDT and patient discussion. We await with interest the results of the Alliance A011202 trial to guide practice in patients having NACT in N1 disease. [1] Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. [2] Giuliano, A.E.; Ballman, K.; McCall, L.; Beitsch, P.; Whitworth, P.W.; Blumencranz, P.; Leitch, A.M.; Saha, S.; Morrow, M.; Hunt, K.K. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann. Surg. 2016, 264, 413–420 Table 1. Demographics and tumour status. Table 2. Patients having Axillary RT. Citation Format: Hamza A. Arabiyat, Iain Brown, Philip Drew, Rachel English, Mona Sulieman, Imran Abbas, Duncan Wheatley, Kali Potiszil, Alastair Thomson, Polly King. Axillary radiotherapy in selected patients with a preoperative diagnosis of lymph node involvement is a safe alternative to axillary lymph node dissection [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 P1-10-17.

Magnetic marker to detect primary lesion and sentinel node in breast cancer. The MAGTOTAL randomised controlled trial.

Background: Several markers have been developed as an alternative to guidewires for non-palpable breast lesion localisation. The study aim was to compare a magnetic marker (seed) with guidewire (wire) for non-palpable breast lesion localisation in combination with a magnetic SLN tracer.