Comparative Analysis of Abbreviated and Full Protocol MRI in Detecting Axillary Lymph Node Metastasis in Patients with Known Breast Cancer

Factors affecting the negative predictive value of positron emission tomography/computed tomography for axillary lymph node staging in breast cancer patients

A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases

623 Background: Neoadjuvant therapy plays an important role in breast cancer treatment. Unlike patients who undergo surgery followed by adjuvant therapy,there are no established guidelines for surgical management following neoadjuvant therapy. Methods: Surgical practice patterns from 50 patients in N0338 “Phase II trial of Docetaxel and Carboplatin administered every two weeks as induction therapy for Stage II and Stage III breast cancer” were reviewed. The protocol did not mandate surgical therapy leaving the decision to the treating surgeon and patient. Results: 66% of patients underwent mastectomy (M) and 33% underwent breast conservation therapy (BCT). Three (9%) had immediate reconstruction. Eight (24%) underwent contralateral prophylactic M. Residual tumor size did not always impact primary surgical therapy. In the M group 4 (12%) had no residual disease, 15 (45%) < 2cm and 14 (42%) > 2cm; whereas, in the BCT group 1 (6%) had no residual disease, 12 (70%) < 2cm and 4 (24%) > 2cm. Axillary lymph node (ALN) staging varied tremendously. Three (6%) patients presented with palpable lymphadenopathy and proceeded to complete axillary lymph node dissection (ALND) after chemotherapy (CT). Fine needle aspiration (8) or core needle biopsy (7) of the axilla was performed in 15 (30%) patients before CT; 1 was negative and went on to have sentinel lymph node biopsy (SLNB) after CT; 14 (94%) were positive with 13 (86%) going on to ALND and 1 SLNB after CT. Five (10%) underwent SLNB prior to CT. One (20%) was positive and went on to have ALND after CT; 4 (8%) were negative and had no further ALN staging. A total of 19 (39%) had SLNB after neoadjuvant therapy; 13 (68%) were positive and underwent ALND; 1 SLNB failed; 2 of 5 that were negative underwent ALND with 1 having a positive lymph node. Ten (20%) underwent ALND with no pre-operative staging with 8 being positive for ALN metastases. Conclusions: Review of study data from multiple institutions revealed no consistent criteria in selection of surgical intervention for the breast tumor or ALN staging. There remains a need for further research in this area to establish standard practice guidelines. Support from NIH, sanofi-aventis, Amgen, Breast Cancer Research Foundation. No significant financial relationships to disclose.

IntroductionMolecular testing for detection of epithelial and/or breast-specific mRNA has the potential to aid in the comprehensive examination of axillary lymph nodes (ALNs) in breast cancer. We evaluated the performance of a One-Step Nucleic Acid Amplification assay (OSNA; Sysmex), an automated assay for detection of cytokeratin 19 mRNA in chemotherapy(CT)-naive and -treated ALNs of breast cancer patients using conventional histopathologic examination (HE) as the gold standard.METHODSALNs obtained from complete axillary dissections were serially sectioned at 1-mm intervals using a proprietary lymph node cutter (Sysmex), and alternate slices were used for OSNA and HE, which included one hematoxylin and eosin stain and a pancytokeratin (CK) immunostain. Isolated tumor cells were classified as micrometastases (MiM) in CT-treated ALNs and as negative in CT-naive ALNs. The presence of tumor cells in either stained preparation was used for categorization of metastatic carcinoma. The agreement between OSNA and HE results for detection of metastatic carcinoma was estimated by using the kappa coefficient for CT-treated and -naive ALN groups separately.RESULTSWe studied 279 ALNs from 39 patients with breast cancer; these included 162 CT-treated and 117 CT-naive ALNs. In the CT-naive group, metastatic carcinoma was detected by HE in 15 of the 117 ALNs (12.8%), 7 classified as micrometastases and 8 as macrometastases. All but 3 of the 7 micrometastases were detected by OSNA. The kappa coefficient between HE and OSNA for this group was 0.87 (95% confidence interval [CI], 0.72–1.00) which implies near perfect agreement between the two methods. In the 162 CT-treated ALNs, metastatic carcinoma was detected in 44, 13 classified as micrometastases and 31 as macrometastases. The results for 17 ALNs in the CT-treated group were discordant between the two methods: 3 ALNs were considered positive by OSNA but negative by HE; 10 ALNs with a mean size of metastasis of 0.5 mm (MiM) and 4 with a mean size of metastasis of 2 mm (macrometastases) were considered positive by HE and negative by OSNA. The kappa coefficient between the two methods for this group was estimated to be 0.71 (95% CI, 0.58–0.84) which implies substantial agreement between the two methods for this group.CONCLUSIONS1. The detection of metastatic carcinoma was highly comparable between the OSNA assay and conventional HE in both CT-naive and -treated ALNs in breast cancer.2. The minimal discordance between HE and OSNA in the results for detection of very small metastases in ALNs in both CT-naïve and –treated groups was most likely the result of tissue-allocation bias.3. The OSNA assay has the potential to be used as either a stand-alone test or integrated with conventional HE for the comprehensive examination of ALNs in breast cancer, thus likely improving current methods of evaluation of ALNs for more accurate axillary staging. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1012.

A review of technical aspects of sentinel lymph node identification for breast cancer.

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

P0192 Sentinel node biopsy in breast cancer using only methylene blue dye: A prospective study in a rural tertiary care centre

The Japanese Breast Cancer Society 2009 Axillary lymph node dissection (ALND) is a standard surgical treatment in patients with involved axillary lymph nodes. Unfortunately, arm lymphedema develops in 2.7– 5.0% of patients treated by partial ALND (level I and II), in 3.1–9.6% of those undergoing total ALND, and in 26– 38% of patients treated with ALND and radiotherapy [1]. The risk of lymphedema is often used as an argument against ALND. Currently, sentinel lymph node (SLN) biopsy has become a highly utilized and widely accepted method for surgical staging of axillary lymph nodes in breast cancer. It can avoid an unnecessary ALND in patients with node-negative breast cancer, thereby pre

616 Background: The current status of axillary lymph node is the most important prognostic factor in breast cancer. Axillary lymph node dissection (ALND) is currently the standard option for assessment of axillary lymph nodes. Positron emission tomography - computerized tomography (PET-CT) imaging and breast sonography are a noninvasive imaging modality that can detect malignant lymph node. The purpose of this study was to evaluate the clinical usefulness of axillary lymph node staging by means of PET-CT imaging compare with breast sonography in breast cancer. Methods: This study involves 129 breast cancer patients and clinically negative axillary node. All patients had whole body PET-CT imaging and breast sonography before SLN biopsy. After SLN biopsy, all patients underwent complete ALND. Axillary lymph nodes were evaluated by standard hematoxylin and eosin staining techniques, while sentinel nodes were further examined for micrometastatic disease. The findings of PET-CT imaging and breast sonography of 129 patients were compared with pathologic findings after operation. Diagnostic accuracy was evaluated applying ROC curve areas. Results: The sensitivity of PET-CT imaging was 60.0%; specificity and accuracy were 83.6% and 73.4%, respectively. The sensitivity, specificity and accuracy of breast sonography were 61.8%, 89.0%, and 77.3% respectively. The SUVs of axillary lymph node ranged from 0.0 to 7.01. Analysis using ROC curves revealed the area under each curve which indicated a diagnostic accuracy. For involvement of axillary lymph node, PET-CT imaging had the area under the curve of 0.735, breast sonography one of 0.769. Conclusions: Axillary lymph node staging using PET-CT imaging is inferior to the breast sonography in early stage of breast cancer patients. Our study reveals the value of PET-CT imaging is not good compare to the breast sonography in the detection of axillary lymph nodes metastasis in patients with early breast cancer. No significant financial relationships to disclose.

Currently, there are limited studies on individualized assessment tools for predicting patients with positive sentinel lymph nodes during breast cancer surgery and exempting axillary lymph node dissection (ALND). Constructing a prediction model based on clinical and pathological features to explore the feasibility of exempting ALND for patients with positive sentinel lymph nodes during breast cancer surgery is of great significance. This study aims to guide the management of axillary lymph nodes in breast cancer patients, so as to ensure the treatment effect while minimizing surgical complications and improving the quality of life of patients. We conducted a retrospective study by collecting data from 133 breast cancer patients who were admitted to the Breast and Thyroid Surgery Department of Liuzhou People's Hospital within the time frame spanning from January 2023 to August 2025. Subsequently, we employed both univariate and multivariate Logistic regression analyses to screen for clinical and pathological features that exhibited a significant association with axillary lymph node metastasis. Based on the identified significant features, we constructed a prediction model aimed at forecasting axillary lymph node metastasis in breast cancer patients. To comprehensively evaluate the predictive performance of the developed model, we utilized receiver operating characteristic (ROC) curves to assess its discriminatory ability, and diagnostic calibration curves to evaluate the accuracy of its predicted probabilities. Multivariate analysis revealed that age, the number of positive sentinel lymph nodes, vascular tumor thrombus, and preoperative axillary lymph node diameter were significantly associated with axillary lymph node metastasis. The ROC curve of the prediction model constructed based on these 4 features showed an area under the curve (AUC) of 0.760, and the diagnostic calibration curve indicated that the model had good fit. The predictive model established based on age, the number of positive sentinel lymph nodes, vascular tumor thrombus, and the preoperative diameter of axillary lymph nodes can preliminarily predict the risk of axillary lymph node metastasis in patients with positive sentinel lymph nodes during breast cancer surgery.

Breast cancer is the most common malignancy among women, leading to approximately 45 000 deaths per annum in the United States (1). The presence of axillary lymph node metastases has major prognostic implications in breast cancer patients (2,3), and it is an important criterion in determining the need for adjuvant chemotherapy (4). Sentinel lymph node (SLN) biopsy has become routine practice in the surgical treatment of patients with breast cancer because the disease status of the SLNs accurately reflects the status of the remaining axillary lymph nodes (5–7). Hence, patients who present with a negative SLN (no metastases) can be spared from having a more traumatic axillary lymph node dissection (ALND), which has been shown to be associated with substantial shortand long-term sequelae (8,9). Despite the enormous advantages of SLN biopsy over ALND in regard to post-operative complications in nodenegative patients, it would be of great clinical benefit if a reliable non-invasive method to assess lymph node status in breast cancer patients could be found. Positron emission tomography (PET) reflects the biochemical and physiologic processes occurring in the tissues being imaged and has been used in diagnosing a variety of malignancies (10, 11). The most frequently used positron emitting radiopharmaceutical is 18-fluor labeled 2-deoxy-D-glucose (F-FDG), a radioactively labeled glucose analog. The clinical use of F-FDG–PET is based on the premise that cancer cells exhibit a higher glycolytic rate than do non-neoplastic cells. Thus, F-FDG accumulates predominantly in the tumor tissue and can be visualized by a PET camera. Since the first reported visualization of lymph node metastases with F-FDG–PET in a preclinical animal study in 1990 (12), several investigations (13–19) have assessed the accuracy of PET in evaluating the nodal status of patients with breast cancer. These investigations have yielded conflicting results, with some investigators doubting that F-FDG–PET is capable of accurately assessing the nodal status of breast cancer patients (13–16) and others believing that a noninvasive PET scan could replace SLN biopsy at predicting the disease status of the axillary lymph nodes (17–19). In a recent investigation by an Italian group (18), preoperative F-FDG–PET was compared with the histologic findings of ALND in 167 clinically node-negative T1 (tumor size 2cm) and T2 (tumor size >2cm to 5cm) breast cancer patients, the largest patient collective published. F-FDG–PET detected 68 of 72 patients with axillary metastases, resulting in an overall sensitivity for PET of 94%. In the subset of T2 patients, the sensitivity was even higher (98%; 48/49), with only one false-negative finding. Based on these results, the authors claimed that F-FDG–PET can safely predict axillary lymph node status in patients with breast cancer and is a reliable and accurate method to identify patients who can avoid ALND. In the second largest published patient collective (19), preoperative F-FDG–PET was compared with the histologic findings of ALND in 124 pT1–T3 (T3 tumor size >5cm) breast cancer patients. PET scanning correctly identified all 44 patients with axillary lymph node metastases, resulting in an overall sensitivity for PET of 100%. These findings led the investigators of that study to suggest that F-FDG–PET should be considered as the initial test in evaluating axillary lymph nodes in breast cancer patients and that those patients without increased axillary F-FDG-uptake may not require ALND. Other investigations (17,20–23) with smaller patient numbers have reported similar findings, with sensitivities of pre-operative F-FDG–PET at detecting axillary lymph-node metastases ranging from 90% to 100%. In contrast to the above-mentioned investigations, several studies have found that F-FDG–PET has a low sensitivity at detecting SLN or axillary lymph node metastases. Indeed, Avril et al. (14) suggest that F-FDG–PET scanning cannot substitute for histologic analyses of axillary lymph nodes. Their study compared the diagnostic potential of F-FDG–PET with ALND in 41 breast cancer patients and reported an overall sensitivity for PET of 79% (19/24). PET sensitivity in the subset of patients with pT1 tumors was, however, only 33%; four of six patients had false-negative results, and the largest metastasis undetected by F-FDG–PET measured 12 mm in diameter. Kelemen et al. (15) also found low PET sensitivity when they compared F-FDG–PET scanning with the histolopathologic findings of SLN biopsies in clinically node-negative T1 and T2 breast cancer patients. If the SLN biopsies were negative by hematoxylin and eosin (H&E) staining, further biopsy sections were obtained for immunohistochemical (IHC) analyses using polyclonal anticytokeratin (CK) antibodies. Four of five patients with SLN metastases had false-negative F-FDG–PET scans (i.e., F-FDG–PET sensitivity was only 20%), and the missed metastases ranged from a micro-metastasis (defined as a cohesive cluster of malignant cells >0.2 mm to 2.0 mm in diameter), which was identified by IHC only, to macro-metastases up to 11 mm in

Axillary lymph node (ALN) metastasis is one of the most important aspects for breast cancer patients’ prognosis; however ALN dissection it is associated with a series of long-term complications. Sentinel lymph node (SLN) biopsy was performed as another procedure to minimize the adverse impact of axillary surgery. Accordingly preoperative prediction of axillary lymph node metastasis (ALNM) by image examination or biopsy of SLN is of great significance to select patients with low risk of ALNM and avoid full axillary lymph node dissection (ALND). In this study, we evaluated preoperative evaluation of sentinel node metastasis by using 18F-FDG PET/CT to staging axillary lymph node status. We undertook a retrospective review of patient data for 275 women who had histologically confirmed breast carcinoma by needle biopsy and underwent 18F-FDG PET/CT examine between March 2015 and April 2018. ALND or SLN biopsy were performed on 268 cases and 18F-FDG PET/CT results were evaluated according to final pathological results. Of 268 patients, 137 cases (79.7%) showed ALNM by surgical histopathology analysis. And we observed that comparing with ALNM group the number of positive lymph node diagnosed by PET/CT in false positive group was significantly lower (P<0.05), while the max diameter of both breast lesion and positive lymph node diagnosed by PET/CT were longer (P<0.05).By using immunohistochemistry staining and classification of molecular subtype of breast cancer, we observed that compared with ALNM group, the ration of HER2 overexpressed breast cancer in false positive group was significantly higher (P<0.05). In conclusion, despite the low false positive rate 18F-FDG PET/CT for preoperative evaluation of sentinel node metastasis is of great value for surgeons to select patients with low risk of ALNM and avoid full ALND.

To discriminate between malignant or benign axillary lymph nodes in breast cancer using MRI, PET-CT, and sentinel lymph node biopsy. Observational study. Department of General Surgery, Recep Tayyip Erdogan University School of Medicine, from January 2014 to March 2019. Sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was carried out on 102 patients, who had locally advanced cases and had not previously received neoadjuvant therapy. Axillary lymph nodes pathology results were evaluated and compared with PET-CT and MRI findings. PET-CT specificity was 93.18%, MRI specificity was 93.75%, and combined PET-CT and MRI specificity was 97.67%. PET-CT sensitivity was 81.03%, MRI sensitivity was 68.57%, and combined PET-CT and MRI sensitivity was 83.05%. For detecting the presence of axillary lymph node metastasis, there was a good correlation between histopathological results and the combined evaluation with PET-CT and MRI (kappa: 0.785, p <0.001). In combined PET-CT and MRI, short diamater mean values of lymph nodes in 10 patients, which could not detect lymph node metastases, were determined to be 5.2 ±0.9 mm. Combining PET-CT and MRI is superior to PET-CT or MRI imaging alone in distinguishing benign and malignant axillary lymph node; and contributes to deciding the approach to axillary lymph node surgery. Lymph node size is also important for this imaging method to determine benign and malignant nodes correctly. Key Words: Breast cancer, PET-CT, MRI, Sentinel lymph node biopsy, Axilla.

Objective Comparing the influence of neoadjuvant chemotherapy on sentinel lymph node biopsy and axillary lymph nodal staging. Methods From June 2005 to June 2007 one hundred and sixty five breast cancer patients of stage Ⅰ,Ⅱa,Ⅱb and Ⅲ underwent sentinel lymph node biopsy(SLNB) using 99mTc combining methylene blue dye as tracer to help axillary lymph node dissection(AND) were retrospectively reviewed. Sixty five patients staged Ⅱb or Ⅲ were treated with three circles neoadjuvant chemotherapy prior to SLNB and AND , another one hundred patients staged ⅠorⅡa had SLNB and AND directly without neoadjuvant chemotherapy.Results Average 14.60 axillary lymph nodes were retrieved in patients had neoadjuvant chemotherapy and 14.74 lymph nodes in patients did not have neoadjuvant chemotherapy(P>0.05),a mean number of 1.46 sentinel lymph nodes in neoadjuvant chemotherapy group and 1.5 sentinel lymph nodes in non-neoadjuvant chemotherapy(P>0.05), sentinel lymph node identification rate 96.9% in neoadjuvant chemotherapy group and 97% in non-neoadjuvant chemotherapy(P>0.05), the false negative rate was 4.6% in neoadjuvant chemotherapy group and 4% in non-neoadjuvant chemotherapy group(P>0.05). Conclusions The mean number of lymph nodes,sentinel lymph nodes,SLN identification rate and false-negative rates after neoadjuvant chemotherapy are similar to those seen in patients without neoadjuvant chemotherapy.The SLNB can accurately predict lymph node status of axillary lymph node following neoadjuvant chemotherapy. Key words: Breast cancer; Sentinel lymph node; Neoadjuvant chemotherapy

The debate regarding the role of lymphadenectomy in breast cancer persists despite the availability of 25-year follow-up data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B04 trial comparing radical mastectomy, total mastectomy with regional nodal irradiation, and total mastectomy with no nodal treatment, a study that was designed to address this question. This trial failed to show a survival benefit attributable to regional nodal surgery or radiation; however, critical review revealed that the trial was likely too underpowered to show this difference, and axillary lymph node dissection (ALND) remained an important component of surgical therapy to accurately stage the axilla, guide systemic therapy decisions, and minimize regional recurrence. Sentinel lymph node (SLN) biopsy, an accurate and less invasive alternative to axillary node dissection, has become the new standard of care for axillary staging, and adoption of this technique has allowed surgeons to avoid axillary dissection and many of its attendant morbidities in node-negative patients. Questions still remain, however, as to whether ALND is always necessary in patients with positive SLNs and considerable effort has gone into the development of nomograms and predictive models to identify a subset of patients with a sufficiently low probability of having additional non-SLN metastases for whom completion node dissection may be avoided. With the early closure of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, it is unlikely that we will have ever have definitive evidence as to whether ALND improves survival in patients with positive lymph nodes; yet axillary lymph node staging remains an integral component of breast cancer treatment, and axillary lymph node status remains the most significant prognostic factor for disease recurrence and survival. All current guidelines for the management of invasive breast cancer include the performance of an axillary staging procedure to guide further treatment decisions, and the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology state that SLN biopsy (SLNB) is the preferred method of axillary sampling when available. NCCN guidelines further state that the performance of ALND is considered optional in patients with ‘‘particularly favorable tumors, patients for whom the selection of adjuvant systemic therapy is likely to be unaffected, for the elderly, and for those with serious comorbid conditions.’’ These caveats allow physicians to balance the risks and the benefits of the procedure for an individual patient, i.e., the art of medicine, but should not result in lesser-quality care for any particular group of patients. In this issue, Halpern et al. have found that significant variation exists in the performance of axillary staging procedures with respect to age, race, and socioeconomic class. Although there is a growing body of literature citing disparities in breast cancer care across race and socioeconomic class, the most significant finding in this analysis of the National Cancer Database (NCDB) is the omission of lymph node biopsy (LNB) in the older population. Patients in the oldest quartile C 73) were more than three times as likely not to receive an axillary staging procedure compared to their younger counterparts (age 51 years). Such variation in axillary surgery in the elderly should not come as a surprise. In the era before SLNB (1985–1995), a NCDB report identified that women older than 70 were more than twice as likely not to receive ALND when undergoing breast-conserving surgery (BCS) for early-stage breast cancer, and after the introduction of SLNB (1998–2005), the authors of the current paper previously reported that among all patients undergoing axillary surgery for earlystage breast cancer, older patients were less likely to receive SLNB (odds ratio, 0.8; 95% confidence interval, 0.78– 0.82). Halpern et al. also cite other published reports of variations in the surgical management of breast cancer for Society of Surgical Oncology 2008