False-negative Rate Of Sentinel Lymph Node Biopsy Research Articles

Intraoperative Nodal Palpation is a Mandatory Component of Sentinel Lymph Node Biopsy for Breast Cancer

Background: In the era of Z-0011, it is mandatory to decrease not only the false negative rate (FNR) of sentinel lymph node (SLN) biopsy but also the risk of residual metastatic nodes after SLN biopsy. Method: SLN biopsy with intraoperative nodal palpation (INP) was performed in patients with clinically node-negative (cN0) breast cancer. All identified blue and hot nodes were removed as blue/hot SLNs, and any suspicious palpable nodes were removed as palpable SLNs. Nodes that were incidentally removed with neighboring the blue/hot SLNs were classified as para-SLNs. Patients with positive SLNs on frozen section underwent axillary lymph node dissection (ALND) except for patients who met the Z-0011 and AMAROS criteria for exemption. Results: Palpable SLNs and para-SLNs were identified in 202 patients. Of 200 patients, excluding 2 patients only with palpable SLNs, 46 patients had involvements of blue/hot SLNs, and 14 had palpable and para-SLNs harboring additional metastasis. When false negative rate (FNR) was calculated based on blue/hot SLNs and palpable SLNs, the additional use of INP resulted in a FNR of 45.2%. Subsequently, ALND was performed in 43 patients with positive blue/hot or palpable SLNs. Residual nodal involvement was found in 28 (65%) of 43 patients after removing blue/hot SLNs. However, after removing palpable SLNs, the rate of residual nodal metastases significantly decreased from 65% (28/43) to 36% (13/36) (p=0.0133). Conclusion: INP decreased both the FNR of SLN biopsy and the risk of residual metastatic nodes after SLN biopsy.

Preoperative prediction of nodal status using clinical data and artificial intelligence derived mammogram features enabling abstention of sentinel lymph node biopsy in breast cancer.

Patients with clinically node-negative breast cancer have a negative sentinel lymph node status (pN0) in approximately 75% of cases and the necessity of routine surgical nodal staging by sentinel lymph node biopsy (SLNB) has been questioned. Previous prediction models for pN0 have included postoperative variables, thus defeating their purpose to spare patients non-beneficial axillary surgery. We aimed to develop a preoperative prediction model for pN0 and to evaluate the contribution of mammographic breast density and mammogram features derived by artificial intelligence for de-escalation of SLNB. This retrospective cohort study included 755 women with primary breast cancer. Mammograms were analyzed by commercially available artificial intelligence and automated systems. The additional predictive value of features was evaluated using logistic regression models including preoperative clinical variables and radiological tumor size. The final model was internally validated using bootstrap and externally validated in a separate cohort. A nomogram for prediction of pN0 was developed. The correlation between pathological tumor size and the preoperative radiological tumor size was calculated. Radiological tumor size was the strongest predictor of pN0 and included in a preoperative prediction model displaying an area under the curve of 0.68 (95% confidence interval: 0.63-0.72) in internal validation and 0.64 (95% confidence interval: 0.59-0.69) in external validation. Although the addition of mammographic features did not improve discrimination, the prediction model provided a 21% SLNB reduction rate when a false negative rate of 10% was accepted, reflecting the accepted false negative rate of SLNB. This study shows that the preoperatively available radiological tumor size might replace pathological tumor size as a key predictor in a preoperative prediction model for pN0. While the overall performance was not improved by mammographic features, one in five patients could be omitted from axillary surgery by applying the preoperative prediction model for nodal status. The nomogram visualizing the model could support preoperative patient-centered decision-making on the management of the axilla.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization

Abstract Background: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of SLNB alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NACT). However optimal methods for TAD are still under investigation. A paramagnetic marker Magseed® was used for the identification of the TLN in this study. Methods: 80 patients eligible to receive NACT were included. All patients had positive axillary lymph nodes verified by core biopsy. Six patients did not receive NACT for any reason. After NACT the targeted lymph nodes (TLNs) were marked with Magseed®, a non-radioactive paramagnetic marker. The SLNs were marked with dual tracer method. The SLNB and the selective TLNB were performed in 74 patients. The Magseed® marked TLNs were identified with the Sentimag® probe and excised. Specimen x-ray was performed to confirm the Magseed® within the prior to NACT biopsied and clipped lymph node. The identification rates of TLNs and SLNs, and the concordance rates were calculated. Results: The TLN identification rate was 100% (74/74), the SLN identification rate was 81.1% (60/74), the concordance rate of TLN and SLN was 58.1% (43/74). In 66.2% (49/74) of the patients the TLN converted to negative, and no ALND was performed. When the TLN converted to negative, a SLN could not be identified in 18.4% (9/49) of the patients. In 33.8% (25/74) of the patients the TLN remained positive after NACT and ALND was performed. When the TLN remained positive, a SLN could not be identified in 40% (10/25) of the patients. Complications according Magseed® deployment or identification could not be observed. Conclusion: Magseed® is a reliable and feasible marker for the identification of TLNs after NACT. Citation Format: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger. Targeted Axillary Dissection with Paramagnetic Marker Localization [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-02.

Abstract PO3-23-01: Triple-tracer Technique for Sentinel Lymph Node Biopsy of Breast Cancer after neoadjuvant Chemotherapy using Blue-dye, Radioisotope combined with Real-time Indocyanine green(ICG) Fluorescence Imaging Procrdures

Abstract Background: For post-neoadjuvant chemotherapy (NAC) patients (pts) with BC, sentinel lymph node biopsy (SNB) was recommended using the dual-tracer mapping technique (radioisotope plus blue dye) or placing a biopsy clip into the positive node at diagnosis and identifying it at the time of surgery due to SN identification rates (IR) were lower and false negative rates (FNR) were greater for pts with local advanced breast cancer (BC) than those of pts with early stage BC in the absence of NAC. Our previous clinical trial has indicated that the real-time ICG fluorescence (RT-ICG) imaging technique could improve the diagnostic sensitivity and detection accuracy for SNB. Methods: Between April 2019 and May 2022, post-NAC SNB were successfully identified in 45 of 52 patients with stage ⅡA to ⅢB (T1-T3, N0-2, M0) who had histologically confirmed breast cancer selected to receive NAC and the standard surgeries were performed after finishing NAC. The SNs was detected by conventional procedures of blue-dye (Indigo carmine) plus 99mTc radioisotope (dual-tracer) and combined with concurrent RT-ICG technique. Clinical node positive (cN+) was diagnosed by the radiologists using axillary ultrasound, MRI and/or CT scan or assessed by fine needle aspiration cytology (FNAC). The positivity of each single SN by each single tracer (blue dye, ICG, or isotope alone) was counted and identified, respectively. All patients are required to undergo SNB followed by completion axillary lymph node dissection (CND). Then the IR and FNR of each single tracer and their summation (triple tracer) were calculated by comparing the results of the SNB and the histopathology of the resection specimens of CND. Results: Among 45 post-NAC pts, the IR and FNR of each single procedure for SNB was 45.7% and 55.6% when used Indigo Carmine blue, 70.3% and 11.1% when used RI, 82.6% and 0 when used ICG fluorescence, respectively. In contrast, the total calculation of triple tracer showed that IR reached to 100% and FNR was 0, respectively. The IR of triple tracer were 83.9% and 100% for ypN0 and ypN(+) pts after NAC, both FNR were 0%. Conclusion: Our results suggested that the triple tracer technique combining blue dye, ICG, and isotope is effective method for detection of SNs in post-neoadjuvant cN+ BC pts. The IR and FNR of SNB might be improved by this multiple tracer mapping technique, particularly for pts with ypN(+) after NAC. It is considered that the multi-tracer can complement each other for what was not able to be traced and detected by the single tracer with one mapping material, and that result in totally the improvement of identification rate of SNB. Citation Format: Hidetaka Watanabe, Yuko Takao, Yuriko Katagiri, Rie Sugihara, Uhi Toh. Triple-tracer Technique for Sentinel Lymph Node Biopsy of Breast Cancer after neoadjuvant Chemotherapy using Blue-dye, Radioisotope combined with Real-time Indocyanine green(ICG) Fluorescence Imaging Procrdures [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-01.

Outcomes of Breast-Conserving Therapy in Patients With Inflammatory Breast Cancer: A Meta-Analysis

IntroductionInflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, patients who respond to neoadjuvant chemotherapy (NAC) are treated with mastectomy and axillary lymph node dissection. This study aimed to synthesize real-world data to evaluate the feasibility of breast-conserving therapy (BCT), sentinel lymph node (SLN), and sentinel lymph node biopsy (SLNB) for patients with IBC who respond to NAC. MethodsPubMed, Embase, and Cochrane Library databases were searched for relevant articles. Clinical studies that compared mastectomy with BCT for IBC treatment were reviewed. The primary outcomes were local recurrence rate and 5-y survival rate in patients with IBC who responded to NAC. Furthermore, the SLN detection rate and false-negative rate (FNR) for SLNB were also evaluated. ResultsIn the final analysis, 17 studies were included. The pooled estimates of the local recurrence rate for mastectomy and no surgical intervention were 18.6% and 15.9%, respectively (P = 0.956). Five-y survival was similar for mastectomy, partial mastectomy, and no surgical intervention (45.8%, 57.1%, and 39.4%, respectively). The pooled estimates of the SLN detection rate and FNR for SLNB were 81.9% and 21.8%, respectively. ConclusionsAmong patients with IBC who respond to NAC, the local recurrence and 5-y survival rates in those undergoing BCT are noninferior to the rates in those undergoing mastectomy; therefore, BCT could be a feasible option for surgical management. However, a poor SLN detection rate and a high FNR were found in patients undergoing SLNB. Further large-scale clinical studies are required to confirm our findings.

Evaluation of Axilla With Sentinel Lymph Node Biopsy (Using Methylene-Blue) and Reverse Axillary Mapping (Using Fluorescein) to Validate Optimum and Safe Axillary Dissection in Breast Cancer.

Introduction Sentinel lymph node biopsy (SLNB) has replaced routine axillary lymph node dissection (ALND) in node-negative axillae. In cases where the axilla needs to be dissected, one must dissect below the uppermost intercostobrachial nerve (ICBN) to avoid damaging arm lymphatics. Methods One milliliter of methylene blue dye was injected around the areola. Fluorescein dye (1 ml) was injected into the upper arm. After SLNB and ALND, the axilla was visualized under blue light. The location of fluorescent lymphatics was mapped with respect to the uppermost ICBN. Results The identification rate of sentinel lymph nodes and arm lymphatics was 100%. Arm lymphatics were above ICBN in 86.7%. The false negative rate of SLNB was 13%, with sensitivity and specificity of 87% and 100%, respectively. Conclusions SLNB using the single-dye technique has results comparable to dual agent studies that utilizeblue dye and radioactive colloid. The uppermost ICBN could define the superior limit of axillary dissection.

The application of contrast-enhanced ultrasound for sentinel lymph node evaluation and mapping in breast cancer patients.

To retrospectively investigate the application of contrast-enhanced ultrasound on sentinel lymph node (SLN-CEUS) for SLN evaluation and mapping in breast cancer patients. Patients diagnosed with breast cancer at the First Affiliated Hospital of Sun Yat-sen University from June 2019 to March 2021 were conveniently evaluated by SLN-CEUS. The results of SLN-CEUS and B mode-ultrasound (BUS) were collected and compared. For patients who only underwent SLN-CEUS, we conducted a 1:1 propensity score matching (PSM). The diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative rate (FNR), false positive rate (FPR), and proportion of undetermined diagnoses were compared between the SLN-CEUS and BUS cohorts. The identification rate and FNR of sentinel lymph node biopsy (SLNB) were also assessed. There were 327 patients in each of the SLN-CEUS and BUS cohorts. Among the entire cohort, both NPV [90.2% (95% CI, 85.4-93.5%) vs. 83.5% (95% CI, 77.8-88.0%), P=0.048] and accuracy [80.7% (95% CI, 76.5-85.0%) vs. 73.7% (95% CI, 68.9-78.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In non-neoadjuvant treatment (NAT) patients, the NPV [94.7% (95% CI, 89.9-97.4%) vs. 85.5% (95% CI, 79.1-90.2%), P=0.007] and accuracy [87.6% (95% CI, 83.2-92.0%) vs. 76.0% (95% CI, 70.4-81.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In NAT patients, no difference in diagnostic efficacy was found. The proportion of undetermined diagnoses of SLN-CEUS was significantly lower than that of BUS (5.8% vs. 15.3%, P<0.001). The identification rate of SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 94.2%, 96.3%, and 89.9%, respectively. The FNR of SLNB with the blue-dye tracer in combination with SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 7.3%, 4.0%, and 12.5%, respectively. Compared to BUS, SLN-CEUS is a better technique for diagnosing SLNs in early breast cancer patients, showing superiority in multiple diagnostic parameters. However, the diagnostic value of SLN-CEUS in NAT patients is still undetermined. SLN-CEUS is a promising mapping method in SLNB, with a high identification rate and a low FNR when used in combination with a blue-dye tracer.

Phase II study on feasibility of sentinel lymph node biopsy for ycN0 patients treated with primary chemotherapy in cT1-3N1M0 breast cancer (SHARE study).

583 Background: Sentinel lymph node biopsy (SLNB)-guided axillary management is still debated for clinically node-positive breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC). Several phase II studies demonstrated high false-negative rates (FNR) in ycN0 BC, but precise diagnostic imaging for nodal involvement may reduce FNR. To explore ideal imaging and lymphatic mapping, the Japanese Society for Sentinel Node Navigation Surgery conducted a prospective non-randomized phase 2 study (SHARE study, UMIN000030558). Methods: Clinical T1-3N1M0 BC was eligible under multimodal imaging of breast ultrasound, CT and/or MR mammography. Nodal metastasis was histologically confirmed. Standard regimen for NAC was performed by physician’s choice. In case of ycN0 BC, SLNB was planned and lymphatic mapping depended on each institutional practice. The primary endpoint is FNR of SLNB and secondary endpoints are the identification rate and outcome of ycN0 BC patients at 2 years after surgery. Moreover, in cases of pN0(sn), pN0(i+)(sn) and pN1mi(sn), SLNB followed by lymph node sampling had been allowed instead of axillary lymph node dissection. Based on an estimated FNR of 5%, 224 patients were needed to give 80% power to reject the null hypothesis that the threshold of FNR is 15% with a one-sided type I error rate of 5%. Results: Between February 2018 and May 2021, 185 patients from 19 institutes were registered. After 27 ineligible cases of protocol deviation, non-ycN0 or withdrawal of SLNB were excluded, 158 ycN0 cases underwent SLNB and sentinel lymph nodes were detected in 153 cases. Among them, the median age was 52 years old. Clinical stage was IIA in 40 cases, IIB in 105 and IIIA in 8. Luminal subtype classified by ER, PR and HER2 expression was found in 60 cases, HER2 in 34, Luminal-HER2 in 35 and triple-negative in 24. Finally, 61 cases had positive nodes, which included 7 false-negative cases. FNR was 11.5% (90% confidence interval, 5.5% and 20.5%). The identification rate was 96.8% and the accuracy rate was 95.4%. Before NAC, multimodal imaging was performed in 148 cases (96.7%) and 1 nodal metastasis was detected in 62 cases (40.5%). When multimodal imaging, 1 nodal metastasis, multiple tracers, multiple sentinel lymph nodes were considered for subset analysis, the FNR was 12.1%, 9.1%, 11.1%, and 10.6%, respectively. If isolated tumor cells in lymph nodes had been defined as pathologically negative even after NAC, the FNR was 7.1%. Conclusions: Multimodal imaging could not improve FNR in ycN0 BC. However, SLNB-guided axillary management should be considered when one positive-node is clinically converted to ycN0 after NAC. We will report the outcome of ycN0 BC cases next year. Clinical trial information: UMIN000030558 .

Abstract P2-14-19: Targeted Axillary Lymph Node Dissections Using Radar Reflector Localization Can Reduce Unnecessary Axillary Lymph Node Dissections in Node Positive Patients Treated with Neoadjuvant Chemotherapy

Abstract Background Targeted axillary dissection (TAD) is a surgical strategy that involves staging the axilla through sentinel lymph node biopsy (SLNB) combined with the removal of a biopsy-proven positive lymph node identified by a clip. TAD reduces the false negative rate of SLNB alone in patients with clinically detected nodal metastasis who receive neoadjuvant chemotherapy (NAC) while avoiding axillary lymph node dissections (ALND). Radar reflector-localization (RRL) can be used to identify previously positive nodes and safely and effectively guide dissection. Methods We performed an institutional retrospective chart review of breast cancer patients with clinical stage T1-3 and N1-3 disease treated with NAC from 2015 to 2020 who had a biopsy proven positive node and underwent TAD using RRL. The primary outcome was the retrieval of clipped node as documented by gross visualization or specimen radiography. Secondary outcomes included pathologic complete response rates and completion axillary lymph node dissections (cALND). Results 79 patients were identified who fulfilled inclusion criteria. 32 (40.5%) had RRL markers placed prior to chemotherapy (mean 187 days prior to surgery) and 47 (59.5%) had RRL markers placed following the completion of chemotherapy (mean 7 days prior to surgery). The clipped node was retrieved in 77 patients (97.5%). 32 of the 34 ypN0 (i+) patients avoided an ALND; 1 patient had a cALND for failure to localize the RRL and 1 patient had a cALND for a false-positive on frozen section. There was no significant difference in clip recovery rates in the pre vs post NAC RRL groups (p=1.00). Conclusion RRL systems are an effective way to guide TAD with a high success rate in identifying and removing previously biopsied nodes. These markers can be placed prior to NAC without migration or deactivation. This strategy allows surgeons to avoid unnecessary cALND. Citation Format: Lilia Lunt, Alison Coogan, Andrea Madrigrano, Cristina O’Donoghue. Targeted Axillary Lymph Node Dissections Using Radar Reflector Localization Can Reduce Unnecessary Axillary Lymph Node Dissections in Node Positive Patients Treated with Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-19.

Abstract P4-07-27: Clipped lymph nodes for cN+ patients decrease false negative rate and lead to potential changes in surgical and oncological management after clinical complete response following neoadjuvant chemotherapy

Abstract Introduction Targeted axillary dissection (TAD) after neoadjuvant chemotherapy (NAC) is a new axillary staging technique that consists of surgical removal of biopsy-proven, positive, clipped axillary nodes (CLN) in addition to the sentinel lymph node biopsy (SLNB), and provides for more conservative axillary surgery1. A question was recently raised whether clipping a positive node for later assessment indeed leads to a management change2. The purpose of our study is to report the feasibility of TAD and to evaluate false negative rate (FNR), impact on surgical ad oncological management. Materials and methods This retrospective, single-institution, study included 73 consecutive women operated between 2019 and 2021 after NAC for cN+ disease confirmed by citology or histology, whose diseased lymph-node was marked with a clip before therapy. At surgery, in case of clinical-radiological complete response, patients underwent TAD (dual mapping with radiocolloid and blue dye + CLN) (n=43), or TAD plus ALND if any residual disease (n=30). The chemoterapeutsic regimen were antracycline/taxane based, with trastuzumab in case of HER2+ tumors. Patients were routinely evaluated with a breast MRI both before and after NAC. Results Clinical and pathological details of the 73 enrolled patients are listed in Table 1. The mean age at diagnosis was 49.53±10 years. Pathologic complete response was achievied in 32 out 73 patients (43.8%) with the greatest rate in HR-/HER2+ tumors (n=10/12; 83.3%). The identification rate of the CLN was 91.8% (68/73), and it was one of SLNs in 68.5% (50/73) of the cases. In cases in which one, two or three or more SLNs were identified, the CLN was in the SLN specimen in 42.9%, 77.8% and 81.8% of cases, respectively. The FNR of the SLN was 18.5% (CI: 4.9-38.1). In 18 cases the CLN was not in the SLN specimen; eleven out of 18 CLNs were positive, leading to ALND, and three of them had additional positive LNs. Only in one case the CLN was negative and the SLN was positive. In 3 cases (4.1%), the CLN was positive in the absence of residual tumour in the breast leading a potential change in the oncological management. Conclusions Removal of CLN after NAC is feasible, allowing de-escalation of surgical management of cN+ women in case of clinical-radiological complete response, as 59% of women avoided a formal ALND. The CLN coincides with SLN in about 70% of cases (more than 80% if three or more SLNs are identified) and reflects the overall status of the axilla in 97.3% of the cases. Adding CLN to SLNB contributes to reduce significantly the FNR of the latter from 18% to 0% (FNR for SLNB =18.5% vs FNR for TAD=0%). Potential changes in surgical (CLN+/SLNs-) and oncological management (CLN+/SLNs- and absence of residual tumor in breast) occurs in 15.1% (11/73) and 4.1% (3/73) of cases, respectively.

Multi-tracer sentinel node biopsy for patients with breast cancer after neoadjuvant chemotherapy

Background: For post-neoadjuvant chemotherapy patients with breast cancer, sentinel lymph node biopsy (SLNB) was recommended using the dual-tracer mapping technique (radioisotope plus blue dye) or placing a biopsy clip into the positive node at diagnosis and identifying it at the time of surgery due to SLN identification rates were lower and false negative rates were greater for patients with local advanced BC than those of patients with early-stage BC in the absence of NAC. Our previous clinical trial has indicated that the real-time ICG fluorescence (RT-ICG) imaging technique could improve the diagnostic sensitivity and detection accuracy for SLNB. Methods: The SLNs was detected by conventional procedures of blue-dye (Indigo carmine) plus 99mTc radioisotope (dual-tracer) and combined with concurrent RT-ICG technique. The positivity of each single SN by each single tracer (blue dye, ICG, or radioisotope alone) was counted and identified, respectively. 51 enrolled cN1patients after NAC are required to undergo SNB followed by completion axillary lymph node dissection (CND). The identification rate and false negative rate of each single tracer and their summation (triple tracer) were calculated by comparing the results of the SLNB and the histopathology of the resection specimens of CND. Results: post-neoadjuvant patients, the identification rate and false negative rate of each single procedure for SLNB was 84.3% and 5.9% when used Indigo Carmine blue, 94.1% and 0 when used ICG fluorescence, 92.2% and 3.9% when used RI, respectively. In contrast, the total calculation of triple tracer showed that identification rate reached to 96.1% and false negative rate was 0, respectively. Conclusions: Our results suggested that the multitracer technique combining blue dye, ICG, and radioisotope is effective method for detection of SLNs in post-neoadjuvant cN+ BC pts. The identification rate and false negative rate of SLNB might be improved by this multiple tracer mapping technique, particularly for patients with ypN(+) after NAC. It is considered that the multi-tracer can complement each other for what was not able to be traced and detected by the single tracer with one mapping material, and that result in totally the improvement of identification rate of SLNB.

Improved false-negative rates using a novel patient selection flowchart in initially biopsy-proven node-positive breast cancer undergoing blue-dye alone guided sentinel lymph node biopsy after neoadjuvant chemotherapy.

Current trials support the application of sentinel lymph node biopsy (SLNB) in node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) with a lower false-negative rate (FNR) if dual-tracer (radioisotope and blue-dye) is used. However, radioisotopes are not available in many areas of the world. In this study, we evaluated the feasibility and accuracy of SLNB mapped with methylene-blue-dye alone. This study enrolled 132 patients with biopsy-proven node-positive breast cancer with a clip placed in the positive node who then received NAC. After chemotherapy and before operation, all patients underwent axillary ultrasound (AUS) assessment and were classified as either negative (AUS-) or positive (AUS +) according to the axillary status. All patients underwent both SLNB and axillary lymph node dissection (ALND). SLNB was mapped with methylene-blue-dye alone. FNRs were evaluated on factors potentially affecting false-negative SLN finding. Using methylene-blue-dye alone, the FNR of SLNB was 9.9%. Post-NAC AUS assessment (p = 0.009) and the number of SLNs retrieved (p = 0.029) showed association with FNRs in multivariate analysis. In AUS- group, FNR was as low as 2.5%. In AUS + group, retrieving ≥ 4 SLNs including the clipped node improved FNR from 17.1% to 4.8%. A flowchart was designed with the combination of post-NAC AUS assessment, retrieved SLN number, and the retrieved of clipped node further improve overall FNR to 3.3%. In biopsy-proven node-positive breast cancer treated with NAC, using a flowchart to optimize patient selection reduces the FNR of single-tracer (methylene-blue-dye) guided SLNB.

Evaluation of indocyanine green combined with methylene blue staining in sentinel lymph node biopsy of breast cancer.

BackgroundMethylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer.MethodsOne hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups.ResultsA total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P<0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P<0.05).ConclusionsICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006)

IntroductionThis study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. MethodsTwo hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. ResultsSurgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. ConclusionSLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Outcomes of Sentinel Node Biopsy for Women with Breast Cancer After Neoadjuvant Therapy: Systematic Review and Meta-Analysis of Real-World Data.

Evidence on the accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) for patients with breast cancer is inconclusive. This study reviewed the real-world data to determine the acceptability of SLNB after NAT. The study searched for articles in the PubMed, EMBASE, and Cochrane Library databases. The primary outcomes were the identification rate for sentinel lymph nodes (SLNs) and the false-negative rate (FNR) for SLNB. The study also evaluated the FNR in subgroups defined by tumor stage, nodal stage, hormone receptor status, human epidermal growth factor receptor-2 status, tumor response, mapping technique, and number of SLNs removed. The study retrieved 61 prospective and 18 retrospective studies with 10,680 initially cN± patients. The pooled estimate of the identification rate was 0.906 (95 % confidence interval [CI], 0.891-0.922), and the pooled FNR was 0.118 (95 % CI, 0.103-0.133). In subgroup analysis, the FNR was significantly higher for the patients with estrogen receptor (ER)-negative status and fewer than three SLNs removed. The FNR did not differ significantly between the patients with and those without complete tumor response. Among the patients with initial clinical negative axillary lymph nodes, the incidence of node metastasis was 26.8 % (275/1041) after NAT. Real-world evidence indicates that the FNR of SLNB after NAT in breast cancer is 11.8 %, exceeding only slightly the commonly adopted threshold of 10 %. The FNR is significantly higher for patients with ER-negative status and removal of fewer than three SLNs. Using a dual tracer and removing at least three SLNs may increase the accuracy of SLNB after NAT.

Treatment of male breast cancer: meta-analysis of real-world evidence.

Breast cancer is rare in men and managed by extrapolating from breast cancer in women. The clinicopathological features of male breast cancer, however, differ from those of female breast cancer. Because clinical trials are rare, the synthesis of real-world data is one method of integrating sufficient evidence on the optimal treatment for this patient population. PubMed, Embase, and Cochrane Library databases were searched. Clinical studies were included if they evaluated the treatments of interest in male breast cancer; these evaluations included breast-conserving surgery (BCS) versus mastectomy, postmastectomy radiation therapy versus no radiation, the accuracy of sentinel lymph node biopsy (SLNB), and a comparison of various endocrine therapies. Forty studies were retrieved. The pooled estimate of overall survival (OS) revealed no difference between BCS and mastectomy groups. Postmastectomy radiation to the chest wall significantly increased OS relative to no postmastectomy radiation (hazard ratio (HR) 0.67, 95 per cent confidence interval 0.54 to 0.84). The pooled estimates of identification and false-negative rates of SLNB were 97.4 and 7.4 per cent respectively. Tamoxifen treatment was associated with significantly increased OS compared with no tamoxifen intake (HR 0.62, 0.41 to 0.95). Identification and false-negative rates for SLNB were comparable to those in female breast cancer. Breast-conserving surgery can be effective and safe; postmastectomy radiation to the chest wall and 5-year tamoxifen treatment improves survival.

Abstract PS1-29: Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound

Abstract Purpose: Neoadjuvant chemotherapy (NAC) has been shown to eradicate axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical approach for these patients to avoid morbidity from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for initially node-positive patients were reported in previous trials. The aim of this study was to evaluate clinicopathological factors and imaging characteristics by MRI and ultrasound (US) as predictors of axillary pathologic complete response (ypN0) after NAC, which enable to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 153 patients with clinically node-positive breast cancer who received NAC from May 2009 to December 2019. Clinicopathological data including age, clinical T/N status, nuclear grade, hormone receptor (HR) and HER2 status were collected. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with cortical thickness (&amp;gt;3.5mm), loss of fatty hilum or round shape (short-axis/long-axis ratio &amp;gt; 0.5) were defined as suspicious lymph nodes. All imaging data were evaluated at baseline and after NAC. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics were assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. Results: The median age was 55.0 (range: 22-79) years and the mean tumor size was 3.86 ± 2.04 cm. Pretherapeutic lymph node status was assessed by FNA in 88 (57.5%) patients. Of 153 patients, 80 (52.3%) patients had luminal, 39 (25.5%) had HER2-positive, and 34 (22.2%) had triple negative disease. Sequential anthracycline and taxane were administered for 138 (90.2%) patients, and 37 (94.9%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 62 (40.5%) patients achieved ypN0. Independent predictors of ypN0 status were breast complete response by MRI (odds ratio [OR]: 9.01, p&amp;lt;0.001), clinical stage N1 (OR: 6.64 vs. cN2-3, p=0.009), absence of lymphadenopathy after NAC (OR: 6.09, p&amp;lt;0.001), HR negativity (OR: 3.10, p=0.02) and HER2 positivity (OR: 2.87, p=0.04). In a model using these predictors, the area under the ROC curve was 0.870 (95% confidence interval: 0.814-0.925, p&amp;lt;0.001). Sensitivity, specificity, positive predictive value and negative predictive value of the model were 72.6%, 86.8%, 78.9% and 82.3%, respectively. After a median follow-up of 49.7 months, 5-year disease-free survival (DFS) was significantly higher in patients who achieved ypN0 than patients with residual axillary disease (88.7% vs. 76.9%, p=0.046). Among 62 patients who achieved ypN0 after NAC, ALND was omitted in 24 (38.7%) patients and irradiation to regional lymph nodes was performed in 8 (33.3%) out of 24 patients. Five-year DFS was comparable between patients with or without ALND (86.8% vs. 91.7%, p=0.815). Conclusions: Our predictive model based on imaging characteristics by MRI and US could help to identify good candidates for omission of ALND after NAC in patients with initially node-positive breast cancer. Citation Format: Akiko Matsumoto, Miki Yamada, Daisuke Tsukahara, Yasuko Umemoto, Hiromitsu Jinno. Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-29.

SPECT-CT visualization and biopsy of sentinel lymph nodes in patients with stage IAB-IIA cervical cancer.

To evaluate the diagnostic accuracy of sentinel lymph node (SLN) biopsy and to determine clinical significance of preoperative single-photon emission computed tomography/computed tomography (SPECT-CT). We retrospectively evaluate data and images of 55 women with stage IAB-IIA cervical cancer that underwent sentinel lymph node biopsy and subsequent lymph node dissection. 99mTc-phytate (300MBq) was injected submucosally in 4 points and SPECT-CT started 2h after the injection. All lymph nodes (LN) that accumulated radiocolloids were regarded as sentinel. Next day after the mapping radical hysterectomy with complete pelvic and parametrial LN dissection and SLN biopsy were performed according to the institute protocol. SPECT-CT identified SLNs in 51 of 55 patients. All SLNs were successfully detected during the surgery. The SLN mapping efficacy was 92.7%. LN metastases were diagnosed in 6/51 (11.8%) cases, including 2 patients with positive SLNs. Sensitivity, negative predictive value (NPV) and false-negative rate for SLN biopsy were as follows: 33.4%, 91.8% and 66.6%. In patients with unilateral SPECT-CT localization of SLNs, LN metastases were identified in 4 (20%) of 20 patients but SLN biopsy was false negative in all cases. In 31 women, SPECT-CT detected SLNs on both sides of the pelvis. In this group, regional LN metastases were diagnosed in 2 patients, and in both cases metastases were detected only in SLNs. In women with SPECT-CT visualization of SLNs on both sides of the pelvis, SLN biopsy had high sensitivity and NPV. In patients with unilateral SLN localization, SLN biopsy cannot be used for the prediction of regional LN status.

Research progress of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer

The feasibility and safety of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for breast cancer are still controversial in clinical practice. SLNB after NAC is feasible and safe for patients with clinically node-negative (cN0) breast cancer, while those with clinically node-positive (cN+ ) should be carefully considered. In addition to methylene blue and 99mTc-sulfur colloid tracing, some other tracing methods have been proposed in clinical studies, such as carbon nanoparticles and indocyanine green fluorescence tracing. The axillary lymph node (ALN) state of SLNB patients after NAC was associated with molecular subtyping, response to chemotherapy, residual breast tumor size, etc. Therefore, a number of factors should be considered to determine whether ALN dissection is needed. The false negative rate of SLNB after NAC can be reduced by some measures such as placing clips prior to surgery and preoperative tattooing with sterile black carbon suspension. Besides ALN, internal mammary lymph nodes is another route for breast cancer metastasis. As a low-invasive diagnostic technique, internal mammary sentinel lymph node biopsy can complete lymph node staging and pathological staging to guide treatment. This review attempts to introduce the research progress of SLNB after NAC from multiple aspects such as feasibility and safety, tracer methods, assessment of ALN status and methods to reduce false negative rate. Key words: Breast neoplasms; Neoadjuvant therapy; Sentinel lymph node biopsy; Axillary lymph node dissection; Internal mammary sentinel lymph node biopsy