Lymph Node Involvement In Breast Cancer Research Articles

Axillary de-escalation after neoadjuvant chemotherapy for advanced lymph node involvement in breast cancer

IntroductionSentinel lymph node biopsy reduces morbidity in patients with clinically node-positive breast cancer who achieve axillary pathologic complete response following neoadjuvant therapy (NACT). De-escalation trials primarily addressed cN1 disease, with underrepresentation of cN2 disease. This study evaluates the role of de-escalation in patients with cN2 breast cancer. MethodsA retrospective analysis of the National Cancer Database (2013–2020) included women over 18 with T1-2 invasive breast cancer and clinical N2 disease who received NACT followed by ALND or SLNB then ALND. The primary outcome was pathologic nodal status post-NACT. ResultsOf 5852 cN2 patients treated, 18.15 ​% achieved ypN0, 0.97 ​% had isolated tumor cells, 19.14 ​% were ypN1, 49.64 ​% were ypN2, and 12.20 ​% were ypN3 following NACT. Achieving ypN0 was associated with pCR in the breast, HER2-positive and triple-negative receptor status, cT2 tumors, and younger age. ConclusionDespite some patients with cN2 disease achieving ypN0, most exhibited residual axillary disease post-NACT. These findings indicate that axillary de-escalation may not be feasible for most patients with cN2 disease, underscoring the importance of meticulous patient selection and assessment.

The Incidence of Breast Cancer Lymph Node Involvement in Trinidad and Tobago.

Objective This study aims to investigate breast cancer lymph node involvement in a West Indian population whilecorrelating it with various histological parameters and evaluating the role of the sentinel lymph node biopsy. Method This is a retrospective study where histology reports for all breast cancer-related biopsies from 2018 to 2021, totaling 813 samples, were obtained. Histological parameters from these reports were extracted into a spreadsheet andanalyzed usingStatistical Product and Service Solutions (SPSS, version 28.0; IBM SPSS Statistics for Windows, Armonk, NY) software for TNM staging and axillary and sentinel lymph node dissections, among other fields found in histology reports. Results In 44.8% of cases, patients present at the T2 stage with associated lymph node spread. Each T stage had more lymph nodes involved than uninvolved for tumors sized T2 and higher. Inversely, for tumors staged under T2, there were generally more uninvolved lymph nodes than involved ones. Larger tumors were found to have advanced N staging, especially in the T3 category, where a significantly higher proportion of cases were found to have N2 and N3 staging compared to the other T stages. This trend is also seen in M staging, where larger tumors metastasize more than smaller tumors (40% for T4a, 0% for T1). Despite significant lymph node involvement being observed, sentinel lymph node biopsies were usually negative. Conclusion More patients in this population present with lymph node involvement than without. Larger breast cancer tumors are associated with greater lymph node involvement, particularly at T2 and higher stages. Sentinel lymph node biopsies can be omitted in smaller breast cancer tumors up to 2 cm in size, and the local recurrence rate is low despite a false-negative rate of around 10% in upfront sentinel lymph node biopsy.

Options to apply national developments in the assessment of sentinel lymph node involvement in breast cancer

Background. Breast cancer is the leading oncopathology of women. The routine radical surgery performed in this pathology includes lymph node dissection, which provokes development of postmastectomy syndrome. However, the removal of non-metastatic lymph nodes is not rational according to the subsequent disability of the patients. This can be avoided by using a sentinel lymph node (SLN) biopsy procedure. At this stage of oncology development, there are several ways to visualize SLN. The fluorescent method is among the most promising. This technique has been used for many years. However, it is not sufficiently implemented in clinical practice. There are still several questions about the procedure for its performance. In addition, it requires the introduction and improvement of domestic developments, including reducing financial costs.Aim. To study the use of indocyanine green of domestic production (LLC Firm “FERMENT”, Russia) and the IC-GOR detection system (LLC “MedKomplekt”, Russia) for SLN biopsy in patients with early breast cancer.Materials and methods. From February to September 2023, biopsy of SLN using indocyanine green (LLC Firm “FERMENT”, Russia) was performed in 53 patients with early breast cancer without clinically detectable lesion of regional lymph nodes. In all cases, according to the clinical examination, the patients had an operable stage of breast cancer (cT1–3N0M0). 5 mg of indocyanine green, dissolved in 4 ml of water for injection, was administered after sanitizing of the surgical field intradermally and subcutaneously at 2 points in the upper-outer quadrant of the breast along the edge of the areola in 40 patients (75.5 %) or paratumorally in 13 patients (24.5 %). An incision in the axilla about 4 cm long was made no earlier than 10–15 minutes after injection of indocyanine green (when visualizing the track 1 cm beyond its distal end to avoid crossing the lymph duct, after which the drug can flow into the wound). After imaging, all detected lymph nodes were removed for planned morphological examination. Standard lymph node dissection of 1 and 2 level was performed in all patients. Middle age of patients was 64.5 years (from 37 to 85 year). In 40 patients (75.5 %) modified radical mastectomy was performed, breast conserving surgery was done in 13 cases (24.5 %).Results. SLN were visualized in 51 patients out of 53 (96.2 %). After the final morphological examination, the majority of patients in the group were ranged in the IA and IIA stages of the disease – 15 (28.3 %) and 28 (52.8 %), respectively. Metastasis in the SLN were found in 9 patients (17.0 %). Besides, in 3 cases (5.7 %) metastasis in the lymph nodes were found after lymph node dissection. In 4 cases (7.6 %) metastasis were found during lymph node dissection but were not detected in the removed SLN. Thus, in the study group 13 (24.5 %) patients had metastatic lymph node lesion despite negative clinical status. The total number of removed SLN in the study group was 169 (from 1 to 6), the average number of removed lymph nodes was 3.3. Any negative events, allergic and general reactions to indocyanine were not reported.Conclusion. Our technique of contrasting SLN with indocyanine green is adequate and reproducible. The frequency of detection of SLN with this method is 96.2 %, with an acceptable level of false negative results is 7.6 %. Indocyanine green (LLC Firm “FERMENT”, Russia) and the LED fluoroscopic cancer detector IC-GOR (LLC “MedKomplekt”, Russia) can be recommended for performing a SLN biopsy.

Predicting Factors Affecting Lymph Node Involvement in Breast Cancer Using Random Forest Approaches

Objectives: The objective of this study was to utilize random forest methodology to develop a practical diagnostic function for predicting lymph node metastasis in patients diagnosed with breast cancer. Methods: The research data of this retrospective cohort study was obtained through a comprehensive analysis of telephone interviews and medical records of 241 patients with breast cancer referred to the hospitals affiliated with Mazandaran University of Medical Sciences between 2016 and 2022. The data analysis method used in this study was random forest analysis to identify the influential factors associated with lymph node metastasis using R software. Results: The mean age of diagnosis for patients was 52.03 ± 10.932. Based on the random forest analysis outcomes, an accuracy rate of 72.2% has been attained. The influential factors in our study included grade, tubule formation, skin involvement, p53 marker, margin involvement, nuclear pleomorphism, Ki67, tumor location, estrogen receptor (ER), and (progesterone receptor) PR markers. These factors were determined to have a significant impact based on the mean accuracy reduction index. Furthermore, the variables that demonstrated significance based on the mean Gini reduction index included age, grade, tubule formation, tumor size, nuclear pleomorphism, disease level, mitosis, skin involvement, tumor location, and margin involvement. Conclusions: The utilization of the random forest algorithm, which demonstrates a favorable level of discriminative capability, may serve as a suitable approach for predicting metastasis in patients with breast cancer. Furthermore, by identifying these factors, experts can employ effective strategies to mitigate the condition.

Accuracy of positron emission tomography-computed tomography in the assessment of metabolically negative axillary lymph nodes in breast cancer

Background Breast cancer is a significant public health concern, and early detection of breast lesions is crucial for improved patient outcomes. Accurate assessment of axillary lymph node involvement in breast cancer is vital for staging and treatment decisions. The purpose of this study was to assess to what extent positron emission tomography (PET)-computed tomography (CT) can be used in the assessment of negative axillary lymph nodes in breast cancer and to determine if pathological variability can affect the result of the PET-CT. Patients and methods This prospective study was carried out on 50 female patients with locally advanced breast cancer and with negative PET-CT scans for active axillary lymph nodes. All studied cases underwent postoperative pathological examination to be compared with preoperative PET-CT results. Results Of the studied cases, 84% showed negative axillary lymph node involvement. PET/CT exhibited high sensitivity (95.24%) and specificity (87.5%) in predicting positive nodes, with an axillary maximum standardized uptake value cutoff value of 4.22 (area under the curve=0.923). Logistic regression revealed a significant association between higher T stage and positive lymph nodes (P<0.05). Conclusion PET/CT demonstrates strong predictive accuracy in detecting metabolically negative axillary lymph nodes in breast cancer patients.

Factors Associated With Node-Positive Disease in Estrogen Receptor-Positive Breast Cancer Patients

IntroductionLarger tumor size and shorter tumor-to-nipple distance at diagnosis are associated with greater risk of lymph node involvement in breast cancer. However, the relationship between receptor subtype status and lymph node metastasis remains unclear. Our objective was to examine the association between primary tumor size, location, and nodal metastasis across estrogen receptor (ER)+/ progesterone receptor (PR)+/ human epidermal growth factor receptor 2 (HER2)-, ER+/PR-/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2+ tumors. MethodsA single-institution retrospective chart review was conducted of breast cancer patients diagnosed between 1998 and 2019 who underwent nodal evaluation during primary surgery. Neoadjuvant chemotherapy, pure ductal carcinoma in situ, inflammatory, recurrent, metastatic, bilateral, multicentric, and multifocal disease were excluded. Descriptive statistics (proportions and frequencies for categorical variables and medians [Q1-Q3] for continuous variables) were used to summarize patient characteristics. Kruskal–Wallis test was applied to test the association of outcome variables and continuous variables. Chi-square test or Fisher exact test was applied to test the association of outcome variables and categorical variables. ResultsSix hundred eighteen ER + patients had a median tumor size of 1.7 cm (1.1-2.5 cm). Two hundred ninety six out of 618 (47.9%) were node-positive and 188/618 (30.4%) had axillary dissection. Eighty four point three percent of patients were ER+/PR+/HER2-, 6.31% were ER+/PR-/HER2-, 6.96% were ER+/PR+/HER2+, and 1.13% were ER+/PR-/HER2+. Median tumor size was significantly larger in node-positive cases compared to node-negative cases in ER+/PR+/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2- subgroups. In ER+/PR+/HER2-patients, median tumor-nipple distance was significantly shorter in node-positive patients compared to node-negative patients. Upper outer quadrant location was significantly associated with nodal positivity in ER+/PR-/HER2- patients. ConclusionsAcross ER + patients, the significance between tumor size, location, and lymph node positivity varied significantly when differentiating by PR and HER2 status.

Identification of a Risk Predictive Signature Based on Genes Associated with Tumor Size and Lymph Node Involvement in Breast Cancer.

Background: Breast cancer is a heterogeneous disease. Small tumors with extensive lymph node involvement (STEL) in breast cancer often reflect a biologically aggressive phenotype and poor prognosis. The aim of this study was to identify key genes associated with STEL and investigate their prognostic values in breast cancer. Methods: RNA sequence data from breast cancer specimens were acquired from The Cancer Genome Atlas (TCGA) database for differential analysis. Weighted gene correlation network analyses (WGCNA) were performed to identify coexpressed gene modules associated with tumor size and lymph node metastases. Gene set enrichment analysis (GSEA) was employed to investigate the biological functions of the identified genes. A combination of LASSO and Cox regression analyses was conducted to establish a risk predictive signature, and time-dependent receiver operating characteristic (tdROC) and Kaplan-Meier analyses were used to evaluate its prediction precision. Quantitative RT-PCR was employed to validate the expression levels of the key genes from the signature set. Results: A total of 2777 genes from three coexpressed gene modules were identified by WGCNA, and 880 differentially expressed genes were identified by transcriptome analyses. The 63 overlapping genes identified by both methods were considered STEL-associated genes, and a 9-gene risk-predictive signature was established based on them, with AUCs at 3, 5, and 7 years reaching 0.810, 0.811, and 0.753, respectively. Conclusion: This study demonstrated the transcriptomic profile of STEL breast cancer and successfully established a risk predictive signature with satisfactory accuracy. These findings may provide insights in to the genetic etiology of breast cancer.

Investigation of p16 protein expression and its association with histopathologic parameters in breast cancer.

We investigated the association between p16 expression and histopathologic parameters including size, neural and vascular invasion, and lymph node involvement in breast cancer. 58 specimens from patients with different grades of breast cancer were included. Hematoxylin and eosin and immunohistochemistry staining for p16 was performed. 5 patients (8.6%) had grade I, 23 (39.7%) had grade II, and 30 (51.7%) had grade III breast cancer. Assessment of the tumor size showed that 5 (8.6%) tumors had a size of ≤2cm, 29 (50%) were between 2-5 cm and 24 (41.4%) had a size of ≥5cm. Moreover, 45 (77.6%) of the included patients had axillary lymph node involvement. Investigation of association between p16 positivity with pathological parameters in three groups with positivity to p16 (1-25%, 26-75%, >75%) showed that there was no association between p16 positivity and other parameters including histologic score (p=0.44), tumor size (p=0.77), neural invasion (p=0.79), perivascular invasion (p=0.98) and the number of involved LNs (p=0.49). From the group including eight patients with >75% p16 positivity, seven (87.5%) were found with neural invasion and two (25%) with perivascular invasion. P16 positivity was not associated with size, neural and vascular invasion, and LN involvement in breast cancer.

Molecular genetic predictors of metastatic lesions of regional lymph nodes in patients with breast cancer

Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (p<0.001) and higher total malignancy score (p<0.001). The groups were also significantly different in tumor location (p = 0.005). Comparative analysis of transcriptome tumor profiling revealed statistically significant differences between groups in the level of expression of three genes: TMEM45A (p = 0.016), CCND1 (p = 0.019), and MIA (p = 0.046). Based on the data obtained we used mathematical modeling and created a predictive model, which with a high degree of probability (AUC = 0.791) allowed to predict the presence of regional lymph nodes metastases in patients with BC.Conclusion. TMEM45A, CCND1 and MIA gene expression in the primary tumor were the markers of lymph node involvement in BC. The developed predictive genetic signature can become an additional diagnostic tool to predict the risk of lymph node metastases at the point of planning the volume of axillary surgery in patients with BC.

Imaging Updates to Breast Cancer Lymph Node Management.

Metastatic lymph node involvement in breast cancer is a key determinant of the overall stage of disease and prognosis. Historically, lymph node status was determined by surgery first, with adjuvant treatments determined based on the results of the final surgical pathologic analysis. While this sequence is still applicable in many cases, neoadjuvant systemic treatment (NST) is increasingly being administered as the initial treatment. In cases that demonstrate good therapeutic response to drug therapies, NST may permit the option to perform less radical surgeries subsequently. Current breast cancer treatment has become multidisciplinary, with overlapping roles from the different disciplines. As surgery may be postponed, imaging and image-guided lymph node interventions have gained importance as the primary means of lymph node assessment. Imaging enables evaluation of all regional nodal basins, including locations where surgery is not usually performed. By differentiating limited versus extensive nodal involvement, imaging findings help determine whether initial treatment should be surgical or medical. If medical treatment with NST is indicated, imaging is performed to monitor the in vivo nodal response to drug therapy and ultimately to help determine the surgical technique to perform on the basis of the final imaging findings after NST. The authors discuss the imaging features of nodal metastases and the indications and techniques for the various image-guided procedures. The relative usefulness and shortcomings of the various imaging examinations are reviewed to discuss how they can be applied when biopsy results are not available. The role of imaging in the multidisciplinary team approach is emphasized based on past clinical trials of lymph node management and recent evolving knowledge of breast cancer staging. Online supplemental material is available for this article. ©RSNA, 2021.

Accuracy of Preoperative Ultrasound-Guided Axillary Lymph Node Core Needle Biopsy to Predict Axillary Lymph Node Involvement in Breast Cancer

Background: Breast cancer operative management consists of breast surgery and axillary lymph node (ALN) assessment. ALN status is an important prognostic factor and determinant of breast cancer treatment. Objective: To investigate preoperative ultrasound-guided axillary lymph node core needle biopsy (USACNB) accuracy in predicting ALN involvement for breast cancer. Materials and Methods: This retrospective cohort study took place between February 2014 and May 2019. One hundred nine consecutive operable breast cancer patients with suspicious ALN involvement were assessed using preoperative USACNB and subsequent breast cancer surgery. Exclusion criteria were insufficient ALN tissue from USACNB for interpretation, previous breast or axillary surgery on the same side. Patients with preoperative histopathology results proving of metastasis underwent ALN dissection (ALND) while those with negative results had sentinel lymph node biopsy (SLNB). When SLNB was positive, ALND was then performed. Preoperative USACNB accuracy was analyzed using SLNB or ALND pathological results as standard tests. Results: The sensitivity, specificity, PPV, and NPV of preoperative USACNB in evaluating ALN involvement was 87.5%, 100%, 100%, and 80.4%, respectively, with an accuracy of 91.7%. Conclusion: Preoperative USACNB shows high diagnostic accuracy in ALN metastasis, but its NPV remains too low to completely rule out ALN involvement. Standard SLNB is still necessary in cases of negative USACNB. Keywords: Breast cancer; Ultrasound guided core needle biopsy; Axillary lymph node

Discordant results in 18F-FDG PET/CT and ultrasound-based assessment for axillary lymph node metastasis detection: A large retrospective analysis in 560 patients with breast cancer

PurposeUltrasound is the recommended modality to assess axillary lymph node involvement in breast cancer; nevertheless, 18F-fluorodeoxyglucose (18F-FDG) integrated positron emission tomography/computed tomography (PET/CT) diagnostic efficiency, to identify suspicious lesions, is also considered. We aim to report discrepancies in ultrasound and 18F-FDG PET/CT results. MethodsThis single-centered retrospective analysis selected consecutive patients with invasive ductal biopsy-proven breast cancer, for whom divergent 18F-FDG PET/CT and axillary ultrasound imaging (and/or core needle biopsy if available) had been performed, and described clinical, histological, imaging, and surgery data. ResultsThis retrospective study included 560 patients and identified discordant results between 18F-FDG PET/CT and ultrasound (suspicious 18F-FDG PET/CT and normal ultrasound imaging and/or core needle biopsy) in 20 (4%) patients. Axillary lymph node involvement was confirmed in 17 (85%) out of these 20 patients. Further, the lymph nodes were smaller than one centimeter in 12 (60%) patients, macrometastasic involvement (involvement >2 mm) was detected in 13 (65%) patients, and more than 3 macrometastases were detected in 6 (30%) patients. All patients had an aggressive breast cancer. The sentinel node biopsy performed in 9 (45%) patients allowed to reveal lymph node involvement, even in cases of macrometastatic involvement. ConclusionDiscordant results were issued from normal ultrasound imaging and/or core needle biopsy, and suspicious 18F-FDG PET/CT revealed that 18F-FDG PET/CT may overcome axillary ultrasound limits in the specific case of aggressive breast cancers, especially for axillary lymph nodes smaller than 1 centimeter. Sentinel node biopsy remains a valuable aid, even in patients with macrometastatic involvement.

Distance Between the Tumour and Nipple as a Predictor of Axillary Lymph Node Involvement in Breast Cancer.

PurposeThe possibility of axillary node metastasis via the lymphatics might be related to a cancer’s location within the breast. Previous studies of this topic had small sample sizes, inaccuracies because of subjective differences, and the inability to depict the entire three-dimensional structure of the breast. Here, we aimed to improve upon these existing drawbacks by retrospectively analysing whether tumour location (quadrants) and tumour–nipple distance can predict axillary node positivity.Patients and MethodsWe identified 961 patients with invasive breast cancer between January 2000 and April 2016. The tumour–nipple distance was objectively measured intraoperatively and clinicopathological information was extracted from hospital database. The distance was measured radially from the nipple to the epicentre rather than the edge of tumour to obviate confounders resulting from tumour size variations.ResultsA total of 847 breast cancers (839 patients) met the eligibility criteria and were included in the statistical analysis. The tumour–nipple distance was smaller in node-positive patients (n = 307; 2.76 ± 2.07 cm) than in node-negative patients (n = 297; 3.41 ± 2.18 cm) (p < 0.001). Tumour–nipple distance was an independent predictor of axillary involvement on logistic regression analysis. However, no statistically significant relationship was detected between node positivity and breast quadrant tumour location.ConclusionTumour–nipple distance can be used to predict axillary lymph node metastasis and assist in surgical decision-making and therapy planning. However, exploratory studies are required to increase our understanding of the mechanism.

P128: Does axillary ultrasound predict the burden of metastatic axillary lymph node involvement in breast cancer?

Introduction: Axillary ultrasound and biopsy of suspicious nodes is used to identify nodal metastasis preoperatively in patients with invasive breast cancer. Patients with preoperatively diagnosed axillary node metastases are advised to undergo axillary node clearance (ANC). Patients with 4 or more positive nodes are offered adjuvant radiotherapy, which may alter patients' primary breast surgery, particularly if considering reconstruction. This study assessed whether axillary ultrasound can predict the number of metastatic axillary nodes.

P012: Targeted SLNB (t-SLNB) using OSNA in breast cancer patients post neoadjuvant chemotherapy

Introduction: Standard management for metastatic axillary nodal involvement in breast cancer has been axillary lymph node dissection (ALND). Neoadjuvant chemotherapy (NACT) has potential to convert to node negative disease sparing morbidity of ALND. Aim to review unit's approach to node positive patients at diagnosis, undergoing NACT.

A Study Correlating the Tumor Site and Size with the Level of Axillary Lymph Node Involvement in Breast Cancer.

Background:Breast cancer is the leading cancer in women. The most common histologic type of breast cancer is infiltrating ductal carcinoma. The mainstay of the treatment of breast cancer is surgery when the tumor is localized, followed by chemotherapy as well as radiotherapy (when indicated) and in estrogen receptor and progesterone receptor positive tumors, adjuvant hormonal therapy.Aims and Objectives:The aim of this study is to correlate tumor site and size with the level of axillary lymph node involvement (ALNI) in early and locally advanced breast cancer.Materials and Methods:This prospective and observational study was conducted on fifty female patients of carcinoma breast with early and locally advanced breast cancer.Results:The age distribution showed two peaks at 41–50 years and 51–60 years with 42 and 24 patients, respectively, in both the age groups. Preoperative lymph node positivity by ultrasonography matched with postoperative histopathological examination (HPE) report. Preoperative ultrasonographically determined tumor size was similar to the final histopathological T stage.Conclusion:As size of tumor increases, there is an increase in ALNI which suggests that nodal metastasis is indicative of tumor chronology. Ultrasonography is a good tool to objectively measure tumor size and lymph node involvement preoperatively. Quadrant of involvement can emerge as a clinically useful prognostic cancer in breast cancer as there is a higher incidence of lymph node positivity with increasing size of the breast tumor and for tumors located at the upper outer quadrant of the breast.

Axillary Lymph Node Involvement in Breast Cancer: A Random Walk Model of Tumor Burden.

We reinvestigate the relationship between axillary lymph node involvement in breast cancer and the overall risk of death. Patients were women from the Surveillance, Epidemiology, and End Results (SEER) program, aged between 50 and 65 years, presenting a first primary T1-T2 (tumor size ≤5 cm), node-positive, non-metastasized unilateral breast carcinoma, diagnosed from 1988 to 1997, treated with mastectomy without radiotherapy. Hazard ratios (HRs) were computed at each percentage of involved nodes using the proportional hazards model, adjusting for the patient's demographic and tumor characteristics. The pattern of the hazard ratios was examined using serial correlations. Significance testing used the "portmanteau" test. Based on 4,387 records available for analysis, the relation between adjusted mortality and axillary lymph node involvement was modeled as Ht - Ht-1 = μ + at, where t is the percentage of involved nodes, Ht is the mortality hazard ratio at the percentage t, μ is a constant, and at is white noise. The constant μ was estimated at 0.020, corresponding to a 2% increment in the mortality hazard ratio per 1% increase in the percentage of positive nodes. The model was considered acceptable by the "portmanteau" test (P=0.205). We conclude that the effect of the tumor burden might be expressed as a random walk difference model, relating the mortality hazard ratio with the percentage of involved nodes. We will use the model to explore how treatments affect the course of the disease.

Nomogram-Based Estimate of Axillary Nodal Involvement in ACOSOG Z0011 (Alliance): Validation and Association with Radiation Protocol Variations and Outcomes

Nomograms may be more accurate than experts at predicting risk. Our aim is to use two validated nomograms for axillary node involvement in breast cancer to assess whether protocol variations occurred in higher risk patients in ACOSOG Z0011. We used the M.D. Anderson (MDA) and Memorial Sloan-Kettering (MSK) nomograms to calculate the estimated risk of additional positive axillary nodes using sentinel lymph node biopsy and primary tumor surgery information. In the control arm, we compared findings of axillary dissection (AD) to nomogram-predicted estimates for validation. Logistic regression was used to evaluate whether nomogram-estimated higher risk of nodal involvement was associated with high tangent (HT) or supraclavicular (SCV) radiation field use for patients with known radiation field design. We included radiation fields in multivariate Cox models to evaluate associations with ten-year local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS). Of the 856 evaluable women enrolled, 552 (64.5%) had complete details for the MDA nomogram. Mean MDA risk estimate for patients in both treatment arms was 23.8%. For patients on the AD arm with positive nodes, the estimated risk was 25.9%. Estimated risk did not significantly differ between treatment arms (p-value 0.16). Higher risk estimate was associated with additional positive nodes in the AD arm (OR: 1.04, 95% CI:1.02-1.06, p<0.0001). 78/165 (47.3%) of evaluable patients in the pooled arms with known radiation fields received either HT(n=53) or SCV(n=25) radiation. We observed significant association with higher MDA nomogram estimated risk and SCV radiation (OR=1.07, 95%CI: 1.04-1.10,p<0.0001) but not HT (OR=0.99, 95%CI:0.96-1.02,p=0.52). On multivariable analysis, MDA nomogram estimate was associated with LRF (HR=1.05, 95%CI:1.02-1.08, p=0.003) but not DFS (HR-1.00, 95%CI:0.9901.02, p=0.54) or OS (HR=1.00, 95%CI:0.99-1.02, p=0.66). Receiving SCV radiation was associated with worse DFS (HR=1.83, 95%CI:0.77-4.36, p=0.045) and OS (HR=2.72, 95%CI:1.03-7.18, p=0.027) but not LRF (p=0.27) The MSK nomogram had similar associations for all endpoints. MDA and MSK nomogram risk estimates were associated with confirmed additional lymph node risk in ACOSOG Z011 in the AD arm and appeared balanced in both arms. Radiation oncologists’ use of SCV fields was associated with treating higher risk patients with a worse prognosis.

Severe decrease in SpO2 and methemoglobinemia following subareolar isosulfan blue administration and clinical relevance.

The level of axillary lymph node involvement in breast cancer is a critical decision factor for adjuvant therapy and the most important indicator of prognosis and survival. Sentinel lymph node biopsy is a minimally invasive technique with low morbidity in axillary staging of breast cancer. Radiocolloid substances (Technetium-99m) and/or blue dyes such as methylene blue or isosulfan blue are used during sentinel lymph node biopsy. Isosulfan blue stain is frequently used in sentinel lymph node biopsy and rarely causes complications. The present case report presents a severe decrease in SpO2 due to methemoglobinemia following isosulfan blue administration as well as skin and urine signs and inconsistency with clinical picture in a 67-year-old, 77 kg, ASA II female case who underwent sentinel lymph node biopsy under general anesthesia.

Isolated Contralateral Axillary Lymph Node Involvement in Breast Cancer Represents a Locally Advanced Disease Not Distant Metastases

BackgroundBreast cancer metastases to an ipsilateral supraclavicular lymph node is assigned a N3 status in the TNM system and thus classified as stage III disease in the American Joint Commission on Cancer staging manual. Breast cancer metastatic to contralateral axillary lymph node (CAM) without metastases to any other distant organ is currently assigned M1 status (stage IV) instead of N3 (stage III). Patients and MethodsWe retrospectively reviewed the medical records of breast cancer patients diagnosed with CAM for their clinical presentation, pathologic diagnoses, treatment, and follow-up data. Patients who had distant metastases at the time of CAM diagnosis were excluded from the study. ResultsWe report 12 breast cancer patients who developed CAM but no evidence of metastases in any other distant organ documented with extensive imaging workup. Imaging studies and thorough pathologic evaluation of the prophylactic total mastectomy specimen did not reveal a primary in the breast to account for the metastases in the axillary node. ConclusionFindings of our study as well as previous studies support that lymph node metastases in the contralateral axilla represents a locoregional spread of the tumor from the index breast via lymphatics rather than hematogenous spread. Therefore, isolated CAM in breast cancer patients should not be classified as stage IV disease.