Breast Cancer Node Research Articles

Comparison of 18F-fluorothymidine Positron Emission Tomography/Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Breast Cancer.

The uptake of 18F-fluorothymidine (18F-FLT) depends on cells’ proliferative rates. We compared the characteristics of 18F-FLT positron emission tomography/computed tomography (PET/CT) with those of 18F-fluorodeoxyglucose (18F-FDG) PET/CT for breast cancer. We prospectively diagnosed patients with breast cancer who underwent 18F-FLT PET/CT and 18F-FDG PET/CT. Subsequently, significant differences and correlation coefficients of the maximum standardized uptake value (SUVmax) in primary breast cancer and axillary lymph nodes were statistically evaluated. We enrolled eight patients with breast cancer. In six treatment-naive patients, the SUVmax for primary lesions showed a significant difference (mean, 2.1 vs. 4.1, p = 0.031) and a strong correlation (r = 0.969) between 18F-FLT and 18F-FDG. Further, although the SUVmax for the axillary lymph nodes did not show a significant difference between 18F-FLT and 18F-FDG (P = 0.246), there was a strong correlation between the two (r = 0.999). In a patient-by-patient study, there were cases in which only 18F-FDG uptake was observed in lymph nodes and normal breasts. Bone metastases demonstrated lower accumulation than bone marrow on the 18F-FLT PET/CT. In conclusion, a strong correlation was observed between the 18F-FLT PET/CT and 18F-FDG PET/CT uptake. Differences in the biochemical characteristics of 18F-FLT and 18F-FDG were reflected in the accumulation differences for breast cancer, metastatic lesions, and normal organs.

Expression of Interleukin-21 and Interleukin-21 receptor in lymphocytes derived from tumor-draining lymph nodes of breast cancer.

Interleukin-21 (IL-21) is produced by various cell types inducing positive and negative effects in immunity against tumors. To investigate the expression of IL-21 by CD4+T and IL-21 receptor (IL-21R) by B lymphocytes isolated from breast-tumor draining lymph nodes (TDLNs). Fresh lymph node samples were obtained from 45 patients with breast cancer. To assess IL-21 expression, mononuclear cells were briefly stimulated whereas IL-21R expression was assessed in unstimulated B cells. Cells were stained with antibodies for CD4, IL-21, CD19 and IL-21R and acquired by flow cytometry. The frequency of IL-21+CD4+T cells did not show significant association with disease parameters. However, the geometric mean fluorescence intensity (gMFI) of IL-21 in CD4+T cells was significantly lower in patients with grade III tumor than grade I + II (P = 0.042). In non-involved LNs, the intensity of IL-21 was significantly higher in patients with stage II compared with stage III (P = 0.038) and correlated negatively with the number of involved LNs. The frequency of IL-21R+CD19+B cells was significantly higher in grade III than grade I + II (P = 0.037). The higher intensity of IL-21 in CD4+T cells showed association with good prognosticators in breast cancer and warrants further investigation of the role played by IL-21 in immunity against breast cancer.

Phosphorylcholine-conjugated gold-molecular clusters improve signal for Lymph Node NIR-II fluorescence imaging in preclinical cancer models

Sentinel lymph node imaging and biopsy is important to clinical assessment of cancer metastasis, and novel non-radioactive lymphographic tracers have been actively pursued over the years. Here, we develop gold molecular clusters (Au25) functionalized by phosphorylcholine (PC) ligands for NIR-II (1000–3000 nm) fluorescence imaging of draining lymph nodes in 4T1 murine breast cancer and CT26 colon cancer tumor mouse models. The Au-phosphorylcholine (Au-PC) probes exhibit ‘super-stealth’ behavior with little interactions with serum proteins, cells and tissues in vivo, which differs from the indocyanine green (ICG) dye. Subcutaneous injection of Au-PC allows lymph node mapping by NIR-II fluorescence imaging at an optimal time of ~ 0.5 − 1 hour postinjection followed by rapid renal clearance. Preclinical NIR-II fluorescence LN imaging with Au-PC affords high signal to background ratios and high safety and biocompatibility, promising for future clinical translation.

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

ObjectivesTo evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer.Materials and methodsWe prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves.ResultsA total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001).ConclusionsCEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer.Key Points• The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis.• The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV).• Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

Single-cell profile of tumor and immune cells in primary breast cancer, sentinel lymph node, and metastatic lymph node.

Little is known about the host-tumor interaction in the lymph-node basin at a single cell level. This study examines single cell sequences in breast cancer nodal metastases of a patient with triple-negative breast cancer. The primary breast tumor, sentinel lymph node, an adjacent lymph node with metastatic involvement and a clinically normal-appearing lymph node were collected during surgery. Single-cell sequencing was performed on all four specimens. 14,016 cells were clustered into 6 cell subpopulations. Cancer cells demonstrated the molecular characteristics of TNBC basal B subtype and highly expressed genes in the MAPK signaling cascade. Tumor-associated macrophages regulated antigen processing and presentation and other immune-related pathways to promote tumor invasion. CD8 + and CD4 + T lymphocytes concentrated more in sentinel lymph node and mainly stratified into two transcriptional states. The immune-cell amount variation among primary tumor, sentinel and normal lymph nodes showed a similar tendency between the sc-RNA-seq profile of TNBC samples and a previous reported bulk RNA-seq profile of a breast cancer cohort, including all four breast cancer subtype samples. Single-cell sequencing analysis suggested that the sentinel lymph node was the initial meeting site of tumor infiltration and immune response, where partial T lymphocytes perform anti-tumor activity, while other T cells exhibit an exhausted state. We proposed a molecular explanation to the well-established clinical principle that the 5-year and 10-year survival outcomes were noninferior between SLND and ALND.

OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial

Background and purposeIn breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. Materials and methodsBC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250–15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). ResultsFive-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI < 5.7%]; non-inferiority p = 0.075). Cumulative Incidences of LRR were 3.5% (INC) and 3.4% (INT) (difference of 0.1% [<4.8%]; p = 0.021), and 5% (INC) and 3.5% (INT) (difference 1.4% [<6.0%]; non-inferiority p = 0.101) for DR. CT was more Incident with INT (26.9%) than with INC (19.2%), though the difference was not statistically significant (HR 1.39 [95% CI: 0.92, 2.10]; p = 0.11). ConclusionIntentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR.Registration Number: ClinicalTrials.gov Identifier: NCT02335957.

Consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) sobre la biopsia selectiva del ganglio centinela (BSGC) y el manejo axilar en el cáncer de mama (2022)

Initial nodal staging is indicated in those cases of breast carcinoma in which the information obtained can change the therapeutic approach or establish prognostic information with implications for patient follow-up.In recent years, the conceptual changes introduced by clinical trials and observational studies have generated new challenges with disparity of criteria regarding the therapeutic approach to be followed in certain cases.This justifies the need to revise the latest consensus document of 2013.Although the main objective of the document is to update clinical practice in sentinel lymph node breast cancer, the changes that have occurred in recent years in the diagnosis and treatment of this tumor make it necessary to include aspects that, although outside the strict scope of the selective sentinel lymph node biopsy procedure, are directly related to it.

Microenvironment components and spatially resolved single-cell transcriptome atlas of breast cancer metastatic axillary lymph nodes.

As an indicator of clinical prognosis, lymph node metastasis of breast cancer has drawn great attention. Many reports have revealed the characteristics of metastatic breast cancer cells, however, the effect of breast cancer cells on the microenvironment components of lymph nodes and spatial transcriptome atlas remains unclear. In this study, by integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, we investigate the transcriptional profiling of six surgically excised lymph node samples and the spatial organization of one positive lymph node. We identify the existence of osteoclast-like giant cells (OGC) which have high expressions of CD68 and CD163, the biomarkers of tumor-associated macrophages (TAMs). Through a spatially resolved transcriptomic method, we find that OGCs are scattered among metastatic breast cancer cells. In the lymph node microenvironment with breast cancer cell infiltration, TAMs are enriched in protumoral pathways including NF-κB signaling pathways and NOD-like receptor signaling pathways. Further subclustering demonstrates the potential differentiation trajectory in which macrophages develop from a state of active chemokine production to a state of active lymphocyte activation. This study is the first to integrate scRNA-seq and spatial transcriptomics in the tumor microenvironment of axillary lymph nodes, offering a systematic approach to delve into breast cancer lymph node metastasis.

Single-cell and spatial transcriptome analyses revealed cell heterogeneity and immune environment alternations in metastatic axillary lymph nodes in breast cancer.

Tumor heterogeneity plays essential roles in developing cancer therapies, including therapies for breast cancer (BC). In addition, it is also very important to understand the relationships between tumor microenvironments and the systematic immune environment. Here, we performed single-cell, VDJ sequencing and spatial transcriptome analyses on tumor and adjacent normal tissue as well as axillar lymph nodes (LNs) and peripheral blood mononuclear cells (PBMCs) from 8 BC patients. We found that myeloid cells exhibited environment-dependent plasticity, where a group of macrophages with both M1 and M2 signatures possessed high tumor specificity spatially and was associated with worse patient survival. Cytotoxic T cells in tumor sites evolved in a separate path from those in the circulatory system. T cell receptor (TCR) repertoires in metastatic LNs showed significant higher consistency with TCRs in tumor than those in nonmetastatic LNs and PBMCs, suggesting the existence of common neo-antigens across metastatic LNs and primary tumor cites. In addition, the immune environment in metastatic LNs had transformed into a tumor-like status, where pro-inflammatory macrophages and exhausted T cells were upregulated, accompanied by a decrease in B cells and neutrophils. Finally, cell interactions showed that cancer-associated fibroblasts (CAFs) contributed most to shaping the immune-suppressive microenvironment, while CD8+ cells were the most signal-responsive cells. This study revealed the cell structures of both micro- and macroenvironments, revealed how different cells diverged in related contexts as well as their prognostic capacities, and displayed a landscape of cell interactions with spatial information.

Evaluation of different imaging modalities for axillary lymph node staging in breast cancer patients to provide a personalized and optimized therapy algorithm

PurposeThe reliable detection of tumor-infiltrated axillary lymph nodes for breast cancer [BC] patients plays a decisive role in further therapy. We aimed to find out whether cross-sectional imaging techniques could improve sensitivity for pretherapeutic axillary staging in nodal-positive BC patients compared to conventional imaging such as mammography and sonography.MethodsData for breast cancer patients with tumor-infiltrated axillary lymph nodes having received surgery between 2014 and 2020 were included in this study.All examinations (sonography, mammography, computed tomography [CT] and magnetic resonance imaging [MRI]) were interpreted by board-certified specialists in radiology. The sensitivity of different imaging modalities was calculated, and binary logistic regression analyses were performed to detect variables influencing the detection of positive lymph nodes.ResultsAll included 382 breast cancer patients had received conventional imaging, while 52.61% of the patients had received cross-sectional imaging.The sensitivity of the combination of all imaging modalities was 68.89%. The combination of MRI and CT showed 63.83% and the combination of sonography and mammography showed 36.11% sensitivity.ConclusionWe could demonstrate that cross-sectional imaging can improve the sensitivity of the detection of tumor-infiltrated axillary lymph nodes in breast cancer patients. Only the safe detection of these lymph nodes at the time of diagnosis enables the evaluation of the response to neoadjuvant therapy, thereby allowing access to prognosis and improving new post-neoadjuvant therapies.

Identification of misdiagnosis by deep neural networks on a histopathologic review of breast cancer lymph node metastases

The frozen section (FS) diagnoses of pathology experts are used in China to determine whether sentinel lymph nodes of breast cancer have metastasis during operation. Direct implementation of a deep neural network (DNN) in clinical practice may be hindered by misdiagnosis of the algorithm, which affects a patient's treatment decision. In this study, we first obtained the prediction result of the commonly used patch-DNN, then we present a relative risk classification and regression tree (RRCART) to identify the misdiagnosed whole-slide images (WSIs) and recommend them to be reviewed by pathologists. Applying this framework to 2362 WSIs of breast cancer lymph node metastasis, test on frozen section results in the mean area under the curve (AUC) reached 0.9851. However, the mean misdiagnosis rate (0.0248), was significantly higher than the pathologists’ misdiagnosis rate (p < 0.01). The RRCART distinguished more than 80% of the WSIs as a high-accuracy group with an average accuracy reached to 0.995, but the difference with the pathologists’ performance was not significant (p > 0.01). However, the other low-accuracy group included most of the misdiagnoses of DNN models. Our research shows that the misdiagnosis from deep learning model can be further enriched by our method, and that the low-accuracy WSIs must be selected for pathologists to review and the high-accuracy ones may be ready for pathologists to give diagnostic reports.

Comparing Early-Stage Breast Cancer Patients with Sentinel Lymph Node Metastasis with and without Completion Axillary Lymph Node Dissection: A Systematic Review and Meta-Analysis.

Currently, the standard method for staging and treatment of axillary lymph nodes for early-stage breast cancer is sentinel lymph node biopsy (SLNB), while axillary lymph node dissection (ALND) is used in cases with palpable axillary lymph nodes or positive SLNB cases. The aim of this review was to compare overall survival (OS), disease-free survival (DFS), and axillary recurrence in early-stage breast cancer patients underwent SLNB or SLNB and completion ALND. The databases of PubMed, Scopus, and Cochrane Library were searched using the key words of "breast cancer", "axillary lymph node dissection", and "sentinel lymph node dissection". In addition, other sources were searched for ongoing studies (i.e., clinicaltrials.gov). The clinical trials were evaluated based on the Jadad quality criteria, and cohort studies were evaluated according to the STROBE criteria. At the end of the search, the articles were screened independently by two reviewers to check their eligibility to be included in the study. Afterwards, the data were extracted independently by two researchers. After searching the databases, 169 papers were retrieved. However, after removing the duplicates and studying the titles and abstracts of these papers, only ten ones underwent further investigation. After reading full-text of each article, four studies were finalized. Following a manual search, 27 papers were entered into the study for the final evaluation, 11 of which were included in the meta-analysis based on the inclusion and exclusion criteria. The findings showed no significant differences in OS, DFS, and axillary recurrence in early-stage breast cancer patients underwent SLNB or SLNB and completion ALND. The findings did not confirm that ALND improved OS, DFS, and axillary recurrence in patients who were clinically node-negative and positive SLNB.

O053 An audit of the diagnostic accuracy of ultrasound-guided fine-needle aspiration of axillary lymph nodes in breast cancer, and its pathological significance to axillary nodal burden

Abstract Introduction Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically, thus the assessment of the axilla with ultrasound should be undertaken if suspicious findings are identified in the breast or axilla. Needle biopsy: (Fine needle aspiration (FNA) or core biopsy (CB) -under imaging guidance- is indicated if enlarged axillary nodes or a mass lesion (U2–5) is identified. Multiple meta-analyses revealed similar specificities between the two methods, however, CB appeared to be more sensitive than FNA when assessing the axilla. Our aim is to detect our breast unit's (ELHT) diagnostic accuracy of US-FNAC of axillary lymph nodes in breast cancer. Methods This was a retrospective audit that looked into all axillary FNAs done in the year 2019. 192 FNAs were evaluated: 23 of which were repeats and only the first FNA was accounted for, 5 were found to be breast masses and were excluded and 4 patients lost to follow up and did not have a final pathology and thus were excluded too. In total, 162 FNAs were examined. Results Multiple accuracy measures were calculated: The absolute sensitivity was found to be 69.69% while the specificity was 86.54% with an absolute diagnostic accuracy of 69.75%. In addition, the false-negative rate was 18.18% and the overall inadequate reports were found to be 12.3%. Conclusion In our breast unit, among this cohort of patients, who had FNAC-axilla, we have reported an overall lower than average sensitivity and specificity rate. Take-home message FNAC for axilla in our trust reported lower than average sensitivity and specificity.

The use of indocyanine green as the only tracer for the identification of the sentinel lymph node in breast cancer: safety and feasibility.

BackgroundSentinel lymph node biopsy (SLNB) is now considered the “gold standard” for axillary staging in the treatment of breast cancer. Most of the lymph node mapping experiences have been performed with a radioisotope (albumin-Tc99m) associated or not with the intraoperative injection of a dye, such as Patent-Blue V. Recent studies have shown how the use of indocyanine green (ICG; a drug used for diagnostic use for many years in other sectors) as a fluorescent tracer, allows to obtain alone detection rate of the sentinel lymph node similar or even better, without the risks related to radioactivity and with better use of resources.MethodsFrom March 2020 to February 2021, 184 patients with breast cancer cN0, candidate for SLNB were enrolled at the Complex Operative Unit (UOC) of Breast Surgery, Breast Unit of the Hospital of Verona. The ICG was injected into the periareolar site and was used the NOVADAQ SPY Elite system (Stryker®) for transcutaneous intraoperative observation of fluorescence. The primary objective of the study is the evaluation of the feasibility of the technique and its sensitivity in the identification of sentinel lymph node; among the secondary endpoints the recognition of predictive factors on the identification (t1-t0) and extraction (t2-t1) times of the sentinel lymph node, and on the number of lymph node uptake pathways. Finally, was analyse the safety of the technique.ResultsThe sentinel lymph node was detected and removed in 98.3%. The average number of sentinel lymph nodes extracted is 1.527, while the average number of total lymph nodes (TLNs) extracted is 3.375. The sensitivity of the sentinel lymph node detection technique with ICG, turns out to be 100%. Finally, in the literature, lymphatic function decreases with increasing age, reducing the identification rate of the SLN; this is not confirmed in our study.ConclusionsOur study confirms the use of the only ICG tracer for SLNB in cN0 breast cancer, demonstrating that it is a safe, effective and sensitive technique, which also allows to reduce costs, risks and organizational efforts.

КЛИНИЧЕСКОЕ ИЗУЧЕНИЕ РАДИОФАРМАЦЕВТИЧЕСКОГО ЛЕКАРСТВЕННОГО ПРЕПАРАТА «НАНОТЕХ, 99mTс» ДЛЯ ВЫЯВЛЕНИЯ СТОРОЖЕВЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ У ПАЦИЕНТОК С РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Purpose: To evaluate the diagnostic efficacy and safety of the use of the radiopharmaceutical drug “Nanotech, 99mTc” in the detection of sentinel lymph nodes (SLN) in malignant breast cancer by indirect radionuclide lymphography and intraoperative radiometry. Material and methods: The results of clinical studies of the drug «Nanotech, 99mTc», conducted in two research centers: N.N.Petrov National Medical Research Center of Oncology (128 patients) and N.N. Blokhin National Medical Research Center of Oncology (20 patients), were analyzed in 148 patients with breast cancer, aimed at sectoral breast resection, radical or subcutaneous mastectomy. The patients included in the clinical trials met all the requirements of the inclusion/non-inclusion criteria assessed at the screening stage. Radiopharmaceutical drug “Nanotech, 99mTc” was injected into the affected mammary gland at 4 mutually perpendicular points intradermally periareolar. The administered activity was 20.0–40.0 MBq for each injection site, the volume of administered drug «Nanotech, 99mTc» was 0.1–0.3 ml for each injection site. The total single administered dose was 80–160 MBq in a volume of 0.4– 1.2 ml. 1–2 hours after administration of the drug, 4–24 hours before surgery, the patients underwent planar polypositional scintigraphy in three standard projections with a marker mark applied to the patient’s skin surface corresponding to the projection of each SLN. The procedure of intraoperative radiometry was performed using a specialized portable gamma detector in the operating room during the main surgical intervention. The main efficiency parameter was the frequency of identification of SLN during intraoperative radiometry, safety indicators were considered adverse events. When evaluating the results, all adverse events that occurred during the study were considered, and their relationship with the drug under study was also evaluated. For statistical analysis, the patients were divided into the following populations: FAS – all patients who received a dose of the finished drug; ITT population – all patients who received a dose of the finished drug and who underwent intraoperative radiometry; PP population – all patients who completed the study in accordance with the protocol. The main efficiency analysis was carried out in the ITT population. The safety analysis was carried out in the FAS population. Results: The frequency of detection of SLN during intraoperative radiometry in 148 patients, in the main efficacy population (ITT), was 142/148 (95.95 %) with a one-sided 95 % confidence interval of 92.24 %, while the width of the lower part of the confidence interval was 3.71 %. Based on the analysis of primary efficacy, a conclusion was made about diagnostic efficacy, since the boundary of the one-sided 95 % confidence interval for the frequency of detection of SLN during intraoperative radiometry exceeds 84 %, while the width of the lower part of the 95 % one-sided interval does not exceed 5 %. When analyzing secondary endpoints in the ITT population, the frequency of detection of hyperfixation foci during diagnostic lymphoscintigraphy was 97.30 % with a one-sided 95 % confidence interval of 93.97 %, while the width of the lower part of the confidence interval was 3.33 %. The results of the analysis of primary and secondary endpoints of diagnostic effectiveness in the PP population were similar to those obtained in the main population of the effectiveness assessment (ITT). The analysis of diagnostic effectiveness, carried out depending on the method of statistical analysis of the primary variable of effectiveness, led to consistent conclusions. No adverse events were registered during the study. The assessment of safety and tolerability based on the results of statistical assessments of vital signs and the condition of the skin at the injection site showed a high degree of safety and tolerability of drug “Nanotech, 99mTc”. Conclusions: This study obtained data confirming the diagnostic efficacy and high degree of safety and tolerability of radiopharmaceutical drug “Nanotech, 99mTc”, which justifies the possibility of its medical use and registration.

The role of sentinel lymph nodes in breast cancer

Introduction. The problem of improving early diagnosis and prognosis of breast cancer remains one of the most actual for current oncological practice. Taking into account a close correlation between the general prevalence of breast neoplasms and mortality from breast cancer, this problem is not only of professional interest, but also has medical-social and socio-economic significance.&#x0D; The purpose of the study is to improve the quality of the sentinel lymph node detection in patients with breast cancer using ICG.&#x0D; Material and methods. At the period 2009–2016, 400 patients with T1-T3N0M0 breast cancer were operated on. All the patients were divided into two groups using two dyes – Patent Blue and ICG. The patients after mastectomy with a sentinel lymph node biopsy had a clinical diagnosis of T2-T3N0M0 breast cancer more often.&#x0D; In group I, 100 patients had the sentinel lymph node biopsy. Lymph node staining was performed using Patent Blue dye.&#x0D; In group II, sentinel lymph nodes biopsy was conducted with the Patent Blue dye and another fluorescent dye — ICG, which was also injected on the affected side of the breast. After ICG dye introduction, in 15 minutes the stained green lymph nodes were detected using special equipment.&#x0D; Criteria for inclusion of patients in the clinical trial:&#x0D; 1) breast cancer patients of any age with T1-3N0M0, I-II AB disease stage;&#x0D; 2) patients with clinically unaffected lymph nodes N0 after examination.&#x0D; Criteria for exclusion of patients from the clinical trial:&#x0D; The exceptions were T3-T4 tumors &gt; 5 cm in diameter, or the skin and chest wall invasion, as well as palpable axillary lymph nodes, 3 or more affected lymph nodes with sentinel lymph node biopsy;&#x0D; 3) patients after radiation therapy.&#x0D; Results. The tumor histology was performed after the node trephine biopsy. The main aims of sentinel nodes detection were staging and improving the breast cancer patients’ life quality after surgical treatment. The post-mastectomy syndrome, the main manifestation of which is swelling of the upper extremity is a big problem for patients because it affects their life quality and disturbs their usual lifestyle. The sentinel lymph node detection, in contrast to axillary lymph node dissection of I-II level, significantly minimizes all the risks of postmastectomy syndrome, in particular, impaired lymphatic drainage in the form of lymphatic edema of the upper extremity, impaired venous outflow in the form of stenoses or the axillary and/or subclavian veins occlusion, rough scars which limit the function of the extremity in the shoulder joint, and brachioplexitis.&#x0D; Conclusions. The study of sentinel lymph nodes significantly improves the results of surgical treatment of breast cancer patients. Based on the clinical-laboratory and histological examinations, new data were obtained concerning the sentinel lymph node detection using two dyes, the choice of the surgical intervention volume and reduction of complications rate at the postoperative period. We found that fluorescent lymphography is highly effective, which allows to recommend it for implementation into the clinical practice. The frequency of sentinel lymph node detection in breast cancer patients is 98% in the control group, 100% – in the main group.&#x0D; On the basis of the obtained results, the sentinel lymph node detection algorithm and the surgical management of patients with breast cancer was developed and implemented into practice, which allowed to reduce the number of complications with using two dyes for the sentinel lymph node detection from 19% to 2% (χ2 =15.37, p&lt;0.001). Recurrence of breast cancer fell from 13% to 8%.

A Novel Hybrid Deep Learning Model for Metastatic Cancer Detection.

Cancer has been found as a heterogeneous disease with various subtypes and aims to destroy the body's normal cells abruptly. As a result, it is essential to detect and prognosis the distinct type of cancer since they may help cancer survivors with treatment in the early stage. It must also divide cancer patients into high- and low-risk groups. While realizing efficient detection of cancer is frequently a time-taking and exhausting task with the high possibility of pathologist errors and previous studies employed data mining and machine learning (ML) techniques to identify cancer, these strategies rely on handcrafted feature extraction techniques that result in incorrect classification. On the contrary, deep learning (DL) is robust in feature extraction and has recently been widely used for classification and detection purposes. This research implemented a novel hybrid AlexNet-gated recurrent unit (AlexNet-GRU) model for the lymph node (LN) breast cancer detection and classification. We have used a well-known Kaggle (PCam) data set to classify LN cancer samples. This study is tested and compared among three models: convolutional neural network GRU (CNN-GRU), CNN long short-term memory (CNN-LSTM), and the proposed AlexNet-GRU. The experimental results indicated that the performance metrics accuracy, precision, sensitivity, and specificity (99.50%, 98.10%, 98.90%, and 97.50) of the proposed model can reduce the pathologist errors that occur during the diagnosis process of incorrect classification and significantly better performance than CNN-GRU and CNN-LSTM models. The proposed model is compared with other recent ML/DL algorithms to analyze the model's efficiency, which reveals that the proposed AlexNet-GRU model is computationally efficient. Also, the proposed model presents its superiority over state-of-the-art methods for LN breast cancer detection and classification.

Abstract 1477: Circulating miR-125a-3p and miR-451a may be liquid biopsy biomarkers for the diagnosis of breast cancer

Abstract Background: Breast cancer is the most prevalent female cancer. Emerging evidence suggests that the unique serum miRNAs can assist in the early detection and diagnosis of breast cancer. Cell-free circulating miRNAs (about 22 nucleotides) are potential diagnostic tools and minimally invasive biomarkers for breast cancer detection. This study aimed to identify specific microRNAs in the serum of patients with breast cancer, which may serve as promising diagnostic and prognostic biomarkers and therapeutic targets. Material and methods: Next-generation sequencing and quantitative real-time PCR (qRT-PCR) array analyses of microRNAs in sera from different subtypes of breast cancer patients and normal female individuals were performed. The differentially expressed microRNAs were verified in serum samples from 100 breast cancer patients. The predictive values of the selected microRNAs were statistically analyzed, determined by the correlation between microRNA expression and tumor parameters. Datasets were graphed using GraphPad Prism Software 8.0. and analysis was done using one-way ANOVA with unpaired two-tailed Student’s t-test. Result: High serum levels of miR-125a-3p and miR-451a were found to be associated with breast cancer tumor subtype, size, and lymph node metastasis. Further functional in vitro experiments and enrichment analysis showed that overexpression and knockdown of miR-451 might significantly affect tumorigenic signaling pathways in TNBC cells. Conclusion: Altogether, our data suggested that serum levels of microRNAs miR-125a-3p and miR-451a can potentially serve as liquid biopsy biomarkers in breast cancer. Citation Format: Hassan Yousefi, Steven C. Eastlack, Jordyn T Fong, Samuel C. Okpechi, Jovanny Zabaleta, Lyndsey R. Buckner, Donnalee N Trapani, Erin Sims, Alison McDaniel McDaniel, Heather Scuderi, Meredith A. Lakey, John T. Cole, Suresh K. Alahari. Circulating miR-125a-3p and miR-451a may be liquid biopsy biomarkers for the diagnosis of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1477.

Efficacy and Safety of Mitoxantrone Hydrochloride Injection for Tracing Axillary Sentinel Nodes in Breast Cancer: A Self-Controlled Clinical Trial.

BackgroundMitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI’s efficacy and safety in sentinel lymph node biopsy (SLNB).MethodsThe trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥−5%.ResultsSLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up.ConclusionsMHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB.Clinical Trial Registration http://www.chinadrugtrials.org.cn, CTR20192435.

Analysis of the Clinical Molecular Characteristics and Neoadjuvant Chemotherapy Response in Patients with Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer and Axillary Lymph Node Metastasis

Objective: This study aimed to investigate the clinical molecular characteristics in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer and axillary lymph node metastasis and explored the related factors of the neoadjuvant chemotherapy (NAC) response. Methods: The data of 185 patients with HER2-negative breast cancer and axillary lymph node metastasis who were treated in the Department of Breast Center of the Affiliated Hospital of Qingdao University from July 2017 to July 2021 were retrospectively analyzed. The clinical features and the related factors for the responses of the primary tumor and axillary lymph node metastasis to NAC were analyzed. Statistical analysis was conducted using the SPSS 26.0 statistical software. Univariate analysis was conducted using the χ2 test, and multivariate analysis was conducted using logistic regression analysis. Results: The differences in estrogen receptor (ER), progesterone receptor (PR), and Ki67 among the three HER2-negative subgroups (the immunohistochemistry (IHC)0 group, IHC1+ group, and IHC2+/in situ hybridization– group) were statistically significant (p &lt; 0.05). Univariate analysis revealed that the differences in the tumor stage, ER, PR, and Ki67 among the groups based on the response of the primary tumor to NAC were statistically significant (p &lt; 0.05), and the differences in ER, PR, and Ki67 among the groups based on the response of axillary lymph node metastasis to NAC were statistically significant (p &lt; 0.05). Multivariate analysis revealed that the difference in Ki67 among the groups based on the response of axillary lymph node metastasis to NAC was statistically significant (p &lt; 0.05). Conclusions: When the expression level of HER2-negative IHC increases, the positive rates of ER and PR increase. A smaller tumor, negative ER, negative PR, and a Ki67 level &gt;30% indicate a good effect of NAC for primary tumors. Negative ER, negative PR, and a Ki67 level &gt;30% indicate a good effect of NAC for axillary lymph node metastasis. Therefore, Ki67 may be an independent factor affecting the efficacy of NAC for axillary lymph node metastasis.