Unnecessary Sentinel Lymph Node Biopsy Research Articles

Radiological and pathological predictors of post-operative upstaging of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma and lymph-nodes metastasis; a potential algorithm for node surgical de-escalation

Background/aimDuctal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma. MethodsWe retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome). ResultsOut of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2–5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1–2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2–2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2–4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4–2.7; p = 0.027).All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old. ConclusionWe identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.

Avoiding unnecessary sentinel lymph node biopsy with the use of superparamagnetic iron oxide mapping agents (Magtrace®) in breast surgery.

Superparamagnetic iron oxide (SPIO) (Magtrace®) is a non-radioactive liquid tracer that can stay in the sentinel lymph nodes for 30 days. Injection of SPIO at time of primary breast surgery where upfront sentinel lymph node biopsy (SLNB) is not immediately indicated allows for a return to theatre if pathology then identifies invasive disease. SLNB is associated with paraesthesia, pain, seroma formation and lymphoedema risk. Hence, our study aims to assess the use of SPIO to avoid upfront SLNB in breast surgery for ductal carcinoma in situ (DCIS) and prophylaxis. Retrospective single-centre study of consecutive patients who underwent injection of SPIO tracer at time of primary breast surgery to avoid upfront SLNB at Chris O'Brien Lifehouse, Sydney, NSW, Australia over a 10-month period. SPIO was injected 38 times, with 34 at time of mastectomy and four cases at time of wide local excision. The indication for surgery was DCIS in 18 cases, risk reduction in 17 cases and other indications in three patients. Six cases (15.8%) required delayed SLNB (D-SLNB) due to the finding of invasive disease on post-operative histopathology. All patients who underwent D-SLNB had nodes successfully localized with SPIO. In our cohort, 84.2% of cases were able to avoid upfront SLNB, and hence avoid the associated complications of SLNB. SPIO injection was successful in localizing the SLN in all cases at time of surgery for D-SLNB. This technique was safe with few associated complications.

Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning: External Validation and Further Model Development.

Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using postoperative data or imaging features that are not part of the diagnostic workup. Lymphovascular invasion (LVI) is a top-ranked predictor of nodal metastasis; however, its preoperative assessment is challenging. This paper aimed to externally validate a multilayer perceptron (MLP) model for noninvasive lymph node staging (NILS) in a large population-based cohort (n=18,633) and develop a new MLP in the same cohort. Data were extracted from the Swedish National Quality Register for Breast Cancer (NKBC, 2014-2017), comprising only routinely and preoperatively available documented clinicopathological variables. A secondary aim was to develop and validate an LVI MLP for imputation of missing LVI status to increase the preoperative feasibility of the original NILS model. Three nonoverlapping cohorts were used for model development and validation. A total of 4 MLPs for nodal status and 1 LVI MLP were developed using 11 to 12 routinely available predictors. Three nodal status models were used to account for the different availabilities of LVI status in the cohorts and external validation in NKBC. The fourth nodal status model was developed for 80% (14,906/18,663) of NKBC cases and validated in the remaining 20% (3727/18,663). Three alternatives for imputation of LVI status were compared. The discriminatory capacity was evaluated using the validation area under the receiver operating characteristics curve (AUC) in 3 of the nodal status models. The clinical feasibility of the models was evaluated using calibration and decision curve analyses. External validation of the original NILS model was performed in NKBC (AUC 0.699, 95% CI 0.690-0.708) with good calibration and the potential of sparing 16% of patients with node-negative disease from SLNB. The LVI model was externally validated (AUC 0.747, 95% CI 0.694-0.799) with good calibration but did not improve the discriminatory performance of the nodal status models. A new nodal status model was developed in NKBC without information on LVI (AUC 0.709, 95% CI: 0.688-0.729), with excellent calibration in the holdout internal validation cohort, resulting in the potential omission of 24% of patients from unnecessary SLNBs. The NILS model was externally validated in NKBC, where the imputation of LVI status did not improve the model's discriminatory performance. A new nodal status model demonstrated the feasibility of using register data comprising only the variables available in the preoperative setting for NILS using machine learning. Future steps include ongoing preoperative validation of the NILS model and extending the model with, for example, mammography images.

A Clinical Decision Tool to Calculate Pretest Probability of Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.

Beyond N Staging in Breast Cancer: Importance of MRI and Ultrasound-based Imaging.

Simple SummaryBreast cancer is the most frequent cancer affecting women and metastatic breast cancer is still the leading cause of death from all cancers in women, accounting for about 3.6% of all deaths in women. The N-stage represents the main prognostic factor affecting the rate of recurrence and the therapeutic management so that a correct staging of the axillary lymph node status is fundamental. Since clinical examination of the axillary cavity is associated with a high false negative rate, reaching values of 45%, the role of imaging becomes crucial to obtain an accurate assessment of loco-regional lymph nodes at the time of diagnosis. In this setting, Ultrasound and Magnetic Resonance Imaging (MRI) represent two important diagnostic tools. In particular, MRI represents an accurate and reproducible technique, which allows an accurate staging of the “N-stage”. The correct N-staging in breast cancer is crucial to tailor treatment and stratify the prognosis. N-staging is based on the number and the localization of suspicious regional nodes on physical examination and/or imaging. Since clinical examination of the axillary cavity is associated with a high false negative rate, imaging modalities play a central role. In the presence of a T1 or T2 tumor and 0–2 suspicious nodes, on imaging at the axillary level I or II, a patient should undergo sentinel lymph node biopsy (SLNB), whereas in the presence of three or more suspicious nodes at the axillary level I or II confirmed by biopsy, they should undergo axillary lymph node dissection (ALND) or neoadjuvant chemotherapy according to a multidisciplinary approach, as well as in the case of internal mammary, supraclavicular, or level III axillary involved lymph nodes. In this scenario, radiological assessment of lymph nodes at the time of diagnosis must be accurate. False positives may preclude a sentinel lymph node in an otherwise eligible woman; in contrast, false negatives may lead to an unnecessary SLNB and the need for a second surgical procedure. In this review, we aim to describe the anatomy of the axilla and breast regional lymph node, and their diagnostic features to discriminate between normal and pathological nodes at Ultrasound (US) and Magnetic Resonance Imaging (MRI). Moreover, the technical aspects, the advantage and limitations of MRI versus US, and the possible future perspectives are also analyzed, through the analysis of the recent literature.

Value of Quantitative SPECT/CT Lymphoscintigraphy in Improving Sentinel Lymph Node Biopsy in Breast Cancer.

Methods We retrospectively enrolled breast cancer patients who underwent SPECT/CT prior to sentinel lymph node biopsy. Quantification of radiotracer uptake from SPECT/CT data was performed. A radioactivity count threshold (RSPECT) using SPECT/CT was calculated for detecting metastatic sentinel lymph nodes. To localize sentinel lymph nodes exactly, we compared the positions of sentinel lymph nodes localized using SPECT/CT with positions localized surgically using an intraoperative γ-probe. Results 491 patients were included, with a median of 3 sentinel lymph nodes/patient detected by the γ-probe and 2 sentinel lymph nodes/patient detected by SPECT/CT. As the number of sentinel lymph nodes visualized on SPECT/CT images, the metastasis incidence of lymph nodes in the ≤2 SLNs group was significantly higher than that in the >2 SLNs group (35% vs. 15%, P < 0.001). No metastasis was found in lymph nodes with RSPECT ≤ 30% in the >2 SLNs group, and thus, 30% (157/526) of SPECT/CT-identified nodes would avoid unnecessary removal. The positions of sentinel lymph nodes localized by SPECT/CT and γ-probe were identical in 42% (39/93) of patients. Conclusions Quantitative Tc-99 m SC SPECT/CT imaging has the potential to preoperatively locate sentinel lymph nodes and intraoperatively avoid unnecessary sentinel lymph node biopsy.

Abstract P3-02-10: Balixafortide-functionalized down-conversion NIR-IIb nanoparticles for lymph node-invaded breast cancer detection

Abstract Introduction:. Breast cancer is the most common malignant tumor in women, which seriously affects the physical and mental health of women. Tumor metastasis detection is the key for tumor staging and therapeutic decision-making as well as prognosis. Since tumor cells spread mainly through lymphatic to distant organs, sentinel lymph node biopsy (SLNB) has emerged as the standard method for staging clinically node-negative breast cancer. During the procedure, pathological methods are needed to evaluate the metastatic status of lymph nodes. However, the sentinel lymph nodes are tumor-free in more than 70% of patients who received SLNB, leading to unnecessary treatments and complications. Hence, how to evaluate the metastatic status of SLN noninvasively and intraoperatively to avoid unnecessary SLNB is a urgent problem to be solved. Nowadays, the gold standard for detection and targeted excision of the sentinel lymph node is preoperative lymphoscintigraphy with technetium-99m or methylene blue. However, the technetium-99m method has radiation hazards.More noteworthy, the operator needs to master learning curve to improve the accuracy of SLNB surgery based on the methylene blue. It is urgent to look for alternative methodologies such as fluorescence-based imaging to improve accuracy of SLNB and overall safety. Noteworthy, the fluorescent imaging in the NIR-IIb window offers greater tissue penetration and contrast compared to conventional imaging, which is more suitable for detecting the metastatic status of SLN in real-time, noninvasively and dynamically in vivo. We have successfully synthesized a targeting CXCR4 probe NaErF4@ NaYF4@PAA@Balixafortide (ErNPs@POL6326). From vivo to vitro, from macro to microscopic, we investigated that the probe has good biocompatibility, specificity and sensitivity. And the probe can assess the status of SLN noninvasively with which fluorescence signal is positively correlated with lymph node metastasis. Methods:. 1. Appearance, stability, fluorescence emission spectrum and penetration were performed to investigate the characterization of the probe. 2. Cytotoxicity assay and pathology of important organs were examined to verify probe safety. 3. Breast cancer cell lines with different expression level of CXCR4 were used to analyze the sensitivity of the probe in vitro. Control probe ErNPs@PAA and free POL6326 blocking assays are used to examine the specificity. 4. 4T1 tumor-bearing mouse modal was performed to investigate the characterization of the probe. 5. Probe was subcutaneously injected into both hind footpad of the Balb/c mice bearing lymphatic metastasis and then fluorescent imaging is taken in the NIR-IIb window. Results:. 1. ErNPs @POL6326 was successfully synthesized with good stability and high intensity of NIR-IIb fluorescent. 2. ErNPs@POL6326 could specifically target different expression level of CXCR4 in breast cancer cell line compared with ErNPs@PAA. 3. ErNPs@POL6326 could specifically accumulate in 4T1 subcutaneous tumor compared with ErNPs@PAA, with tumor-to-background ratiomaximized at 36 h post injection. 4. In living mice with SLN metastasis of 4T1 tumors showed that ErNPs @POL6326 could easily drain into SLN and target to the metastatic 4T1 tumor cells, resulting in strong fluorescence signals. Summary:. Our results demonstrate that ErNPs @POL6326 can noninvasively and dynamically evaluate the status of SLN in real-time and confirm that fluorescence signal is positively correlated with lymph node metastasis. In the future, we will conduct in-depth analysis the long term toxicology of ErNPs @POL6326 in vivo. In summary, we believe that these results will provide research basis for optimizing the current diagnosis and treatment process of SLNB and improving the accuracy of diagnosis and treatment. Citation Format: Yuan-Yuan Zhu, Yong-Qu Zhang, Zun Wang, Min Chen, Guo-Jun Zhang. Balixafortide-functionalized down-conversion NIR-IIb nanoparticles for lymph node-invaded breast cancer detection [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-10.

The validity and clinical utility of axillary ultrasonography-guided fine needle aspiration biopsy in detection of nodal metastasis in early-stage breast cancer patients: a retrospective single-center experience.

Assessing the validity and clinical utility of axillary ultrasonography (AUS)-guided fine needle aspiration biopsy (FNAB) in detection of nodal metastasis during preoperative axillary investigation in comparison to the histopathologic diagnosis in early-stage breast cancer. A total of 279 operated primary breast cancer patients (age: 55.3 ± 12.8, ranged 17-90 years) were included. Data on AUS findings at the time of initial diagnosis (first look AUS), second-look AUS findings performed by the breast radiologist during breast biopsy procedure and the AUS-guided FNAB findings were evaluated with respect to the final histopathology report obtained through axillary surgery via sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND). The diagnostic performance of each method in detecting metastatic ALNs were compared in terms of sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). The sensitivity, specificity, and accuracy of the first look AUS in detecting nodal metastasis were 64.56%, 86.78%, and 74.19% while the PPV and NPV were 86.44% and 65.22%, respectively. The sensitivity, specificity, and accuracy of the second-look AUS were 70.25%, 87.60%, and 77.78%, while PPV and NPV were 88.10% and 69.28%, respectively. The sensitivity, specificity, and accuracy of the second-look AUS guided FNAB were 89.19%, 73.33%, and 87.30%, while the PPV and NPV were 96.12% and 47.83%, respectively. The consideration of second-look AUS and finding of nodal metastasis in FNAB was associated with significantly higher likelihood of ALND (55.4% vs. 44.6%, p < 0.001) and lower likelihood of SLNB (34.7% vs. 65.3%, p < 0.001) compared to consideration of nonmetastatic ALN status. In 23 (22.3%) patients with positive findings on AUS-guided FNAB, SLNB was applied; 21 had positive results after surgical dissection, indicating that nearly 20% of patients had unnecessary SLNB. US-guided FNAB of suspicious ALNs is a simple, minimally invasive, and highly effective method for preoperative axillary staging in patients with invasive breast cancer avoiding the more invasive method SLNB and it enables the surgeon to proceed directly to ALND in positive cases.

27573 A clinical decision tool to calculate probability of sentinel lymph node metastasis in cutaneous melanoma

Objective: Sentinel lymph node status is a strong prognostic indicator for patients with cutaneous melanoma and is used to select patients for adjuvant therapy. However, unnecessary sentinel lymph node biopsy (SLNB) specimens have substantial cost and morbidity burden. Previous attempts to predict SLNB outcomes have relied on single-institution data and/or gene expression testing. Here we present Expected Lymphatic Metastasis Outcome (ELMO; https://melanoma-sentinel.herokuapp.com/), the first personalized clinical decision-making tool developed using nationally representative data with clinically actionable probability thresholds.

Establishment of a preoperative prediction model for axillary lymph node burden in patients with early breast cancer

Objective: To explore the method of predicting high lymph node load in patients with early breast cancer to avoid unnecessary sentinel lymph node biopsy. Methods: The clinicopathological and thoracic multi-slice spiral CT (MSCT) data of 2620 patients with early (cT1~2N0M0) breast cancer treated in the Affiliated Cancer Hospital of Zhengzhou University from January 1, 2014 to August 1, 2018 were collected. According to the postoperative pathological results, the patients were divided into the group with axillaryhigh lymph node burden (HNB) and the non-HNB group. The influencing factors of axillary lymph node burden in patients with early breast cancer were determined by univariate and multivariate analysis, and the diagnostic model of MSCT to HNB was established. The best cutoff value for the diagnosis of HNB was determined through analyzing the receiver operative characteristic (ROC) curve, and the consistency between MSCT diagnosis and pathological diagnosis was evaluated by Kappa test. Results: Among the 2 620 patients, 168 were diagnosed of HNB. Univariate analysis showed that the tumor size, the status of human epidermal growth factor receptor 2 (HER-2), the number of abnormal lymph nodes showed in MSCT, the ratio of the length to the diameter of the maximum abnormal lymph node as shown in MSCT, the condition of the maximum abnormal lymph node door, and the parenchyma of the maximum abnormal lymph node were related to axillary lymph node burden in patients with early breast cancer (P<0.05). Multivariate analysis showed that the number of abnormal lymph nodes showed in MSCT was an independent influencing factor of axillary HNB in patients with early breast cancer. Compared with patients without abnormal lymph nodes, the OR values of patients with 1, 2, 3 or more abnormal lymph nodes displayed by MSCT and in axillary HNB status were 3.305, 9.379, 126.163 and 780.953, respectively. Using 3 or more abnormal lymph nodes detected by MSCT to predict the area under the ROC curve of axillary HNB in patients with early breast cancer, the area was 0.928, the sensitivity was 82.1%, the specificity was 95.4%, and the accuracy was 94.5%. Kappa test showed that the consistency between MSCT diagnosis and pathological diagnosis was relatively high (Kappa=0.629, P<0.001). Conclusions: The number of abnormal lymph nodes showed in MSCT is an independent influencing factor of axillary HNB in patients with early breast cancer. Taking 3 or more abnormal lymph nodes showed in MSCT as the threshold can help to predict the axillary HNB status of early breast cancer patients and exempt some of them from unnecessary sentinel lymph node biopsy.

Establishing a prediction model of axillary nodal burden based on the combination of CT and ultrasound findings and the clinicopathological features in patients with early-stage breast cancer.

Axillary lymph node (ALN) management in early-stage breast cancer (ESBC) patients has become less invasive during the past decades. Here, we tried to explore whether high nodal burden (HNB) in ESBC patients could be predicted preoperatively, so as to avoid unnecessary sentinel lymph node biopsy (SLNB). The clinicopathological and imaging data of patients with early invasive breast cancer (cT1-2N0M0) were analyzed retrospectively. Univariate and multivariate analyses were performed for the risk factors of axillary HNB in ESBC patients, and a risk prediction model of HNB was established. HNB was identified in 105 (8.0%) of 1,300 ESBC patients. Multivariate analysis showed that estrogen receptors (ER) status, human epidermal growth factor receptor 2 (HER2) status, number of abnormal lymph nodes (LNs) on computed tomography (CT), and axillary score on ultrasound (US) were the risk factors of HNB (all P<0.05). The area under the receiver operating characteristic (ROC) curve in the prediction model was 0.914, with the sensitivity being 85.7% and the specificity being 82.4%. The calibration curve showed that the prediction model had good performance. As a valuable tool for predicting HNB in ESBC patients, this newly established model helps clinicians to make reasonable axillary surgery decisions and thus avoid unnecessary SLNB.

Combining the Ultrasound Features of Primary Tumor and Axillary Lymph Nodes Can Reduce False-Negative Rate during the Prediction of High Axillary Node Burden in BI-RADS Category 4 or 5 Breast Cancer Lesions

The purpose of this study was to determine whether incorporation of the ultrasound (US) features of the primary tumor and axillary lymph node (ALN) could improve the prediction of high axillary nodal burden (HNB) and, thus, avoid unnecessary sentinel lymph node biopsy (SLNB). A total of 347 patients with Breast Imaging Reporting and Data System US category 4 or 5 breast cancer lesions were included. Their pre-operative US features and post-operative pathologic results were collected. The patients were then divided into the following groups based on surgical histology: limited nodal burden (LNB: 0–2 LNs involved) and heavy nodal burden (HNB: ≥3 metastatic LNs). Univariate and multivariate logistic regression analyses were conducted to determine the most valuable variables for HNB prediction. Receiver operating characteristic curves were obtained to assess their values. We found that a non-circumscribed margin, cortical thickness (≥3 mm) and number (≥3) of suspicious ALNs are indicators for HNB prediction. The false-negative rate (FNR) in model 1 (cortical thickness + number of suspicious ALNs) was 15.5% versus 3.4% in model 2 (non-circumscribed margin + cortical thickness + number of suspicious ALNs). Our results indicate that combining the US features of the primary tumor and ALNs can reduce the FNR during HNB prediction.

Preoperative conventional axillary ultrasound (AUS) and sonoelastography (SE) for predicting axillary lymph node metastasis in breast cancer patients.

e12074 Background: Patients with operable breast cancer (BC) and clinically negative lymph nodes (CNLN) usually undergo sentinel lymph node biopsy (SNLB) or axillary lymph nodes dissection (ALND). AUS followed by fine-needle aspiration (FNA) or core-needle biopsy (CNB) could decrease number of unnecessary SNLBs and allow to assign patient to ALND directly. On the other hand, new AUS techniques such as SWE could enhance AUS specificity and allow to avoid SNLB in some patients. Aim: To assess sensitivity, specificity and negative predictive value of the AUS+SWE followed by FNA or CNB in patients with operable BC. Methods: Since Sep 2012 to Jan 2018 150 pts with operable BC and were enrolled. We include 30 pts in training cohort with clinically positive lymph nodes to verify AUS+SWE sensitivity and specificity. In validation cohort only those pts who were candidates for SNLB and who presented with tumor staging up to T3, and clinically negative axillae were included (n=120). All patients underwent preoperative AUS in B-mode, SWE, followed by FNA or CNB in case of suspicious nodes were detected. All pts underwent axilla surgery (SNLB = 46, ALND =74) and final pathology outcomes were available for all pts. Results: In training cohort of 30 patients with clinically positive lymph nodes the overall AUS+SWE sensitivity was set at 89.2%. The positive predictive value was calculated to be 96.1%. In the assessment of invasive breast tumors stages T1- T3 with clinically negative lymph nodes the sensitivity was 74.2%, specificity 95.5% positive predictive value was 85.2% and negative predictive value 91.4% If FNA or CNB follow the AUS+SWE in patients with CNLN the sensitivity was 86.7%, specificity 85.7% positive predictive value was 92.8% and negative predictive value was 75% (FNA or CNB was performed in 40 patients of 120 in validation set). Area under the ROC-curve was calculated as 0.860 [95% CI 0.766 to 0.954] for the US+SWE and 0.705 [95% CI 0.581 to 0.828] for the US+SWE followed by FNA or CNB. Conclusions: Axillary US+SWE should be included in the preoperative staging of all patients with invasive breast cancer. The addition US+SWE (not obviously followed by FNA or CNB) could lead to avoiding of unnecessary SNLB or ALND in patients with clinically and pathologically negative lymph nodes with negative predictive value of 91.4%. On the other hand in patients with US+SWE positive lymph nodes SNLB could also be skipped and the time interval to definitive therapy became shorter. Clinical trial information: BCA_US_SWE_001.

Abstract P1-15-13: Sentinel lymph node biopsy after neoadjuvant chemo therapy in patients with clinically node negative breast cancer: Can sentinel lymph node biopsy be omitted in selected tumor subtypes?

Abstract Background Selected patients presenting with clinically node negative breast cancer (cN0) stage II-III can be treated with neoadjuvant chemo therapy (NCT) followed by surgery of the breast and sentinel lymph node biopsy (SLNB). Pathological response rates are known to vary by tumor subtype with complete pathological response up to 60% in both ER-, HER2-positive tumors and triple-negative (TN) tumors. However, hormone receptor-positive, HER2-negative tumors exhibits lower response rates to NCT. About 70-80% of the patients with a clinically negative axilla, also have pathologically negative axilla after NCT. Properly selecting those patients with a low probability of sentinel lymph node (SLN) metastasis after NCT might save them an unnecessary SLNB. The aim of our study was to assess the impact of tumor subtypes on final pathologic node (pN) status in patients with clinically node negative (cN0) breast cancer who underwent NCT. Methods All cN0 patients diagnosed from 2014-2017 in one large teaching hospital in the Netherlands who were treated with NCT and subsequent surgery including SLNB were selected. This retrospective cohort contained a series of 107 patients with 105 tumors treated for stage II-III breast cancer resp. stage 2 (n=107) and stage 3 (n=2), all cN0. Patient age, tumor size, uni/multifocality at presentation did not differs across subtypes. Histological grading and histological type at presentation did differ across subtypes. Approximated subtype was TN in 21 (19.3 %), HER2-positive in 34 (31.2%), and hormone-receptor-positive, HER2-negative in 54 (49.5%) patients. Results In a total of 109 tumors, 88 had a negative post-NCT SLNB (80.7%), 4 had isolated tumor cells (3.7%) 7 had micro metastasis (6.4%), 10 had macro metastasis (9.2%). Rates of pathological nodal negativity were significantly higher in patients with TN (100%) and HER2-positive tumors (97.1%) than in those with hormone-receptor-positive, HER2-negative tumors (63%) (p&amp;lt; 0.001). Furthermore, a total of 41 (37.6%) patients had a complete pathologic response (pCR) of the primary breast tumor of which 40 (97.6%) had pathologically confirmed negative SLN and 1 (2.4%) had isolated tumor cells. A total of 67 patients had no pCR of which 48 (71.6%) had pathologically confirmed negative SLN and 19 (28.4%) were SLN positive (p &amp;lt; 0.001). Rates of pCR were significantly higher in HER2-positive (70.6%) and TN tumors (47.6%) than in those with hormone-receptor-positive, HER2-negative tumors (13.0%) (p&amp;lt; 0.001). Conclusion SLNB after NCT might be considered to be omitted in patients presenting with cN0 with TN and HER2+ tumors, as SLN is rarely positive. Furthermore, SLN was rarely found positive in patients who achieved pCR. However, more data are necessary for multivariate logistic regression and definite conclusions. Citation Format: Beijert IJ, Francken A, Honkoop AH, Noorda EM. Sentinel lymph node biopsy after neoadjuvant chemo therapy in patients with clinically node negative breast cancer: Can sentinel lymph node biopsy be omitted in selected tumor subtypes? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-13.

Abstract P3-03-20: Which biopsy is preferred to stage the axilla under ultrasound guidance in early breast cancer patients: Fine-needle aspiration cytology or core needle biopsy?

Abstract Background: Preoperative axillary ultrasound (AUS) offers the potential to identify clinically axillary negative patients with axillary lymph node (ALN) metastasis directly to axillary lymph node dissection (ALND) with avoid of unnecessary sentinel lymph node biopsy (SLNB) except Z0011 candidates. Which biopsy should be preferred is pendent with lack of enough prospective studies. The purpose of our study was to compare the accuracy of ultrasound guided fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) for the designated ALN prospectively. Methods: Consecutive patients with histologically confirmed breast cancer from April, 2010 to December, 2014 were preliminary screened for our study. All the candidate patients were prospectively assessed by ipsilateral AUS before initial treatment regardless of clinical ALN status.Abnormal lymph nodes were characterized by round shape with uniform or eccentric thickening, focal bulging or irregularity of the cortex displacement, obliteration of the hilum; or total loss of recognizable lymph node architecture. If suspicious ALN was identified, both ultrasound-guided FNAC and CNB were performed for the same designated ALN.The diameter in longitudinal section, transverse section and maximum cortical thickness of the target node was recorded. When more than one abnormal lymph node was present, the most abnormal-appearing node was sampled. The target tissue for biopsy was hypoechoic thickened cortex. Patients with a positive FNAC/CNB underwent ALND, and those with a negative FNAC and CNB biopsy or without suspicious ALN by AUS underwent SLNB. The paired parameters of FNAC and CNB were compared using McNemar's exact test. Results: 705 consecutive patients were screened and 558 patients (561 axillae) underwent AUS evaluation with confirmed ALN pathological results.145 patients (146 axillae) with both FNAC and CNB were finally enrolled. Final histopathological results showed that 83.6% (122/146) were node positive (5 micro-metastases were considered negative). Sensitivity of FNAC and CNB was 67.2% (82/122) and 91.8% (112/122). Overall accuracy of FNAC and CNB was 72.6% (106/146) and 93.2% (136/146). Negative predictive value (NPV) of FNAC and CNB was 37.5% (24/64) and 70.6% (24/34). There was significant difference in sensitivity, overall accuracy and NPV between FNAC and CNB (p&amp;lt;0.001). 80.6% (29/36) FNAC negative and CNB positive patients have ALN cortical thickness of 3.3-7.2 mm. Conclusion: CNB is more sensitive and accurate than FNAC to stage the axilla under ultrasound guidance in operable breast cancer patients, especially in patients with ALN cortical thickness of 3.3-7.2 mm. Citation Format: Zhou M, Qiu J, Chen J, Hu Y, Deng Y, Zheng S. Which biopsy is preferred to stage the axilla under ultrasound guidance in early breast cancer patients: Fine-needle aspiration cytology or core needle biopsy? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-20.

Axillary ultrasound and fine needle aspiration biopsy in the preoperative diagnosis of axillary metastases in early‑stage breast cancer

The efficacy of axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) has been questioned. The present study was performed to determine the sensitivity, specificity and accuracy of axillary ultrasound (US) and fine needle aspiration biopsy (FNAB) in the diagnosis of axillary metastases in patients with early breast cancer. A total of 214 patients with stage I and II breast cancer between June 2015 and January 2017 were included. All of the patients received axillary US as a primary investigation for lymph node status. US-guided FNAB was performed on suspicious lymph nodes. Those with non-suspicious and FNAB-negative axillary nodes proceeded to SLNB at the time of primary breast surgery. ALND was performed when the result of the US-guided FNAB was positive. The results of US and cytology were compared to histopathological results to determine their sensitivity, specificity, positive and negative predictive value and accuracy. A total of 76 out of 214 patients (35.5%) had axillary lymph node metastases at final histology. The sensitivity and specificity of axillary US alone were 59.2% (45/76) and 78.3% (108/138), respectively. Axillary US with FNAB identified 32 patients with positive lymph node metastases, and increased the sensitivity and specificity to 71.1% (32/45) and 100.0% (30/30). Combined with FNAB, the positive and negative predictive values were 100.0% (32/32) and 69.8% (30/43), respectively. Axillary US-alone or combined US/FNAB had a high accuracy rate and a satisfactory result as they cost less and it is easy to assess the status of axillary lymph nodes. Thus, axillary US with FNAB may avoid unnecessary SLNB in a significant number of patients.

105(PB-006) - Effective use of pre-operative axillary ultrasound and core biopsy can avoid unnecessary sentinel lymph node biopsy procedure

105(PB-006) - Effective use of pre-operative axillary ultrasound and core biopsy can avoid unnecessary sentinel lymph node biopsy procedure

Re: Predictive value of fine needle aspiration biopsy of axillary lymph nodes in preoperative breast cancer staging.

Axillary management in breast cancer has evolved tremendously in the last decades. Sentinel lymph node biopsy (SLNB) has replaced axillary dissection in patients without any clinical and radiological involvement in the axilla. Although the complication rate of SLNB is lower than axillary dissection, the search for an accurate method to determine the axillary status in breast cancer with even lower complication rate is continuing. Fine needle aspiration biopsy (FNAB) is performed under ultrasonography guidance in case of suspicious lymph nodes in the axilla, especially in those with cortical thickening or decreased echogenecity in the hilum in addition to changes in size and shape of the lymph node. The accuracy of FNAB in predicting the status of the axilla is investigated in recent studies. Fine needle aspiration biopsy of the axilla helps the clinician in determining surgical approach and neoadjuvant chemotherapy. Nowadays, extent of axillary surgery has almost no definitive role in deciding the mode of adjuvant treatment. Obtaining information about the presence of metastatic disease in the axilla is enough to determine the prognosis of the patient. However, 30% of axillary metastases were detected with FNAB under ultrasonography guidance and additional 30% with SLNB whereas the axillary status of the remaining patients were determined by histopathologic examination (1). In addition to the information about the axilla, FNAB enables us to place clips into the metastatic lymph nodes to follow the results of neoadjuvant treatment. Akinci et al. investigated this topic in the article entitled “Predictive value of fine needle aspiration biopsy of axillary lymph nodes in preoperative breast cancer staging” (2). This study aimed to determine the role of ultrasound-guided FNAB in axillary staging. Sensitivity, specificity, positive and negative predictive value, and accuracy of FNAB were studied. Sensitivity and negative predictive value showed moderate values (60%) whereas specificity and positive predictive values were 100%. Overall accuracy of axillary FNAB was reported as 76.1%. These results are in accordance with the results of the previous studies. Sensitivity of FNAB under ultrasound guidance changes between 45–95% and the specificity is almost 100% (3, 4). Microbiopsies using larger needles and addition of immunohistochemical examination increase the sensitivity and presence of micrometastases in the lymph node contributes to the false negative results (5). Small number of patients included in the study may be its limitation, however, prospective design of the study supports the results with higher reliability. Finally, this study encourages the clinicians to utilize ultrasound-guided FNAB more frequently to avoid unnecessary SLNB in breast cancer. As a conclusion, randomized controlled trials including large enough number of patients are required to establish the value of FNAB in axillary staging of breast cancer. Sentinel node vs. observation after axillary ultrasound (SOUND) trial is an ongoing prospective randomized trial comparing SLNB and no axillary surgery in patients with normal axillary ultrasound (6). If a high predictive power of FNAB for axillary lymph node metastases could be proven, SLNB might be replaced by this method in the future. Detection of axillary metastases with FNAB might avoid performing SLNB and frozen section study decreasing time spent during surgery and total expenses in treatment.

Evaluation of axillary involvement by ultrasound-guided lymph node biopsy: A prospective study

ObjectivesThe primary aim of this prospective study was to evaluate the accuracy of pre-operative ultrasound (US) alone and associated with a fine needle aspiration cytology (FNAC) or a core needle biopsy (CNB) in the diagnosis of axillary node involvement in patient with breast cancer. The secondary study objective was to determine if this US±FNAC or CNB can lead to the adequate axillary surgery in cN0 and cN1 patient. MethodsA total of 121 consecutive women with stage cT1 to cT2, cN0/cN1, invasive breast cancer were prospectively identified at our institution between February 2, 2013 and August 30, 2013. The sensitivity, specificity, VPP, NPV were calculated, with confidence intervals, using the definitive histological result of the sentinel node biopsy (SLNB) or axillary lymph node dissection (ALND) as the baseline. ResultsTwenty-seven CNB and 2 FNAC were performed. For the whole series, the sensitivity and the specificity of US alone were 48.7% [36–59%] and 89% [83–94%]. For US±FNAC or CNB, the sensitivity and the specificity were 35.9% [26–38%] and 98.8% [94–100%]. Seven women with cN1 clinical examination had SLNB, which permit to decrease the number of ALND of 16.3%. It would have avoided unnecessary SLNB, prompting immediate ALND in 9 patients with cN0 axillae, which means a reduction of SLNB of 8.6%. US±FNAC or CNB lead to the adequate surgery in 72.7% of cases. ConclusionUS±CNB or FNAC is also a relatively efficient and safe test and should be considered routinely. It allowed triaging patients to the well axillary surgery (SLNB or ALND).

P311 How to avoid unnecessary sentinel node biopsy in patients with ductal cancer in situ

P311 How to avoid unnecessary sentinel node biopsy in patients with ductal cancer in situ