Positive Sentinel Lymph Node Biopsy Research Articles

Is Axillary Lymph Node Dissection Needed? Clinicopathological Correlation in a Series of 224 Neoadjuvant Chemotherapy-Treated Node-Positive Breast Cancers

Axillary lymph node status is valuable in determining systemic and radiation therapy. Following neoadjuvant therapy for patients with clinically involved axillary nodes, the role of axillary lymph node dissection (ALND) following a positive sentinel lymph node biopsy (SLNB) is a subject of controversy. We retrospectively analyzed 224 neoadjuvant chemotherapy-treated node-positive breast cancer cases and evaluated the role of ALND in optimizing staging accuracy and treatment outcomes. 63 (27.8%) underwent ALND based on post neoadjuvant persistent positive lymph nodes on exam /imaging. SLNBs were performed in 161 (71.9%) patients as initial surgical planning; 67 (41.6%) patients had positive SLNB results, and 51 (76.1%) underwent further ALND. In patients with one positive sentinel lymph node, follow-up ALND yielded additional positive lymph nodes in 10.5% of cases, whereas in patients with two or more positive sentinel lymph nodes, follow-up ALND yielded additional positive lymph nodes in 87.5% of cases. The presence of 2 positive macro-metastatic sentinel lymph nodes significantly predicts additional nodal involvement, especially in patients without a pathologic complete response. De-escalation of axillary surgery to SLNB alone in this context may be safely considered in neoadjuvant-treated clinical node positive patient with <2 positive sentinel lymph nodes. Our findings help guide surgeons to appropriately select patients who can potentially benefit from ALND for locoregional control and recommendation for adjuvant radiation.MicroabstractWe retrospectively analyzed 224 neoadjuvant chemotherapy-treated node-positive breast cancer cases and found that in patients with one positive sentinel lymph node, follow-up ALND yielded additional positive lymph nodes in 10.5% of cases, whereas in patients with two or more positive sentinel lymph nodes, follow-up ALND yielded additional positive lymph nodes in 87.5% of cases. The presence of 2 positive macro-metastatic sentinel lymph nodes significantly predicts additional nodal involvement, especially in patients without a pathologic complete response. Our findings help guide surgeons to appropriately select patients who can potentially benefit from ALND.

Prediction of non-sentinel lymph node metastases in T1–2 sentinel lymph node-positive breast cancer patients undergoing mastectomy following neoadjuvant therapy

BackgroundAxillary lymph node dissection (ALND) is the standard axillary management for breast cancer patients with positive sentinel lymph node biopsy (SLNB) after neoadjuvant therapy. Nevertheless, when that happens, the frequency of additional positive nodes is not properly evaluated. We aim to develop a prediction model to assess the frequency of additional nodal disease after a positive sentinel lymph node following neoadjuvant therapy.MethodsWe retrospectively analyzed the ultrasound and clinicopathological characteristics of breast cancer patients with 1–3 positive sentinel lymph nodes (SLN) undergoing mastectomy after neoadjuvant therapy (NAT) at our institution, and performed univariate and multivariate logistic analyses to confirm the factors affecting non-SLN metastasis. These factors were included to establish a nomogram, and the area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were utilized to assess the validity of this model.ResultsA total of 126 breast cancer patients were ultimately included in our study, 38 (53.5%) patients were diagnosed with non-SLN metastases of all 71 patients in training set. The results of multifactorial logistic analysis suggested that lymph node metastasis ratio (LNR), short axis of lymph node and progesterone receptor (PR) were strongly associated with non-SLN metastasis. We established a nomogram using the above three variables as predictors, which yielded an area under the curve of 0.795, and validated with a favorable AUC of 0.876.ConclusionThe nomogram we constructed can accurately predict the likelihood of non-SLN metastasis in our patients with 1–3 positive SLN after NAT, which may help guide decision making regarding axillary management.

ThP1.12 - Axillary Node Clearance Following Positive Sentinel Node Biopsy: Is it Always Necessary?

Abstract Aim The study was carried out to determine what proportion of patients have residual disease on completion Axillary node clearance (ANC) following positive nodes on prior Sentinel node biopsy (SNB) and assess for correlation between possible predicting factors such as neoadjuvant chemotherapy and the absence of positive nodes at ANC. Methods Operation records of patients who had surgery for breast cancer were used to identify all patients who had Axillary node clearance done from 2020 to 2023. Patients who did not have SNB prior to ANC were excluded. Results Less than 45% of patients had residual disease on completion ANC. Data was evenly spread between ductal carcinoma and lobular carcinoma on biopsy. There was no significant correlation found between number of positive nodes found at SNB and positive nodes at ANC. More than 50% of patients who had neoadjuvant chemotherapy prior to procedure were node-negative on completion ANC. Conclusion Management of axillary disease post positive SNB remains debatable. Use of neoadjuvant chemotherapy may reduce the need for completion axillary node clearance.

Treatment Patterns and Outcomes of Stage III Melanoma Patients with Positive Sentinel Lymph Node Biopsy: A Real-Life Experience.

Background: Advancements in managing stage III melanoma have involved the implementation of adjuvant therapies alongside a simultaneous decrease in the utilization of completion lymph node dissection (CLND) following positive sentinel node biopsy (SLNB). Methods: This retrospective study from the University of Turin's Dermatology Clinic analyzed relapse-free survival (RFS) and overall survival (OS) among stage III melanoma patients (n = 157) who underwent CLND after positive SLNB versus those who did not receive such procedure. Results: Patients without CLND had a median RFS of 49 months (95% CI 42-NA), while CLND recipients showed 51 months (95% CI 31-NA) (p = 0.139). The 48-month OS for non-CLND patients was 79.8% (95% CI 58.2-91.0) versus 79.2% (95% CI 67.5-87.0) for CLND recipients (p = 0.463). Adjusted Hazard Ratios through inverse probability treatment weighting revealed the impact of CLND to be insignificant on RFS (aHR 0.90, 95% CI 0.37-2.22) and marginal on OS (aHR 0.41, 95% CI 0.13-1.21). Conversely, adjuvant therapy significantly reduced the risk of relapse (aHR 0.46, 95% CI 0.25-0.84), irrespective of CLND. Conclusions: This study corroborates the growing evidence that CLND after positive SLNB does not enhance RFS or OS, while emphasizing the crucial role of adjuvant therapy, be it immunotherapy or targeted therapy, in reducing the risk of relapse in melanoma patients with positive SLNB.

A Comprehensive Analysis of Metastatic Disease following Surgery for Clinically Localized Cutaneous Melanoma.

The NCCN considers "baseline staging" (whole body CT or PET scan +/- brain MRI) for all asymptomatic melanoma patients with a positive sentinel lymph node biopsy. The true yield of these workups is unknown. We created cohorts of adult malignant melanoma patients, using the National Cancer Database (2012-2020) to mimic three common scenarios: (1) clinically node negative, with positive sentinel lymph node(s) (SLNB[+]); (2) clinically node negative, with negative sentinel lymph node(s) (SLNB[-]); (3) clinically node positive with confirmed lymph node metastases (cN[+] and pN[+]). Multivariable regression, supervised decision trees, and nomograms were constructed to assess the risk of metastases based on key features. 10,371 patients were SLNB[+], 55,172 were SLNB[-], and 4,012 were cN[+] and pN[+]. The proportion of patients with any metastatic disease (brain metastases) were as follows: SLNB[+]: 1.4% (0.3%); SLNB[-] 0.3% (<0.1%); cN[+] and pN[+] 11.6% (1.6%). On multivariable regression, Breslow depth > 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for SLNB[+] and SLNB[-] patients found the only groups with >2% risk of metastases were T4 tumors or T2/T3 tumors with ulceration and LVI. Most groups had a negligible risk (<0.1%) of brain metastases. This is the first large analysis to guide the use of imaging for cutaneous melanoma. Among clinically node negative patients, metastatic disease is uncommon and brain metastases are exceedingly rare. Further investigation could promote a tailored approach to metastatic workups guided by individual risk factors.

54814 Mitotic Rate is More Important than Breslow Thickness for Predicting Sentinel Lymph Node Biopsy Positivity and Melanoma-Associated Survival for T1 Cutaneous Malignant Melanoma Cases

54814 Mitotic Rate is More Important than Breslow Thickness for Predicting Sentinel Lymph Node Biopsy Positivity and Melanoma-Associated Survival for T1 Cutaneous Malignant Melanoma Cases

Triple-Negative Breast Cancer in Older Patients: Does SLNB Guide Therapy?

Older breast cancer patients represent a heterogeneous population. Studies demonstrate that sentinel lymph node biopsy (SLNB) omission may be appropriate in some clinical scenarios, yet patients with triple-negative breast cancer (TNBC) are often excluded from these studies. This study evaluated differences in treatment and survival for older patients with TNBC based on SLNB receipt and result. Patients 70 years old or older with a diagnosis of cT1-2/cN0/M0 TNBC (2010-2019) who underwent surgery were selected from the National Cancer Database. Logistic regression estimated the association of SLNB with therapy, and Cox proportional hazards models estimated the association of SLNB with overall survival (OS) after adjustment for select factors. Of the 15,167 patients included in the study (median age, 77 years), 13.02% did not undergo SLNB, 5.14% had pN1 disease, 0.12% had pN2 disease, and 0.01% had pN3 disease. Most of the patients (83.9%) underwent surgery first, and 16.1% received neoadjuvant chemotherapy. Of those who underwent surgery first and SLNB, 6.2% had pN+ disease. Receipt of SLNB was associated with a higher likelihood of chemotherapy (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.55-2.21), regardless of pN status. Compared with those who did not undergo a SLNB, a negative SLNB was significantly associated with lower mortality (hazard ratio [HR] 0.68; 95% CI 0.63-0.75), although there was no difference for a positive SLNB (HR 1.14; 95% CI 0.98-1.34). The patients receiving chemotherapy first showed no difference in survival based on SLNB receipt or result (p = 0.23). Most older patients with TNBC do not have nodal involvement and do not receive chemotherapy. The receipt and results of SLNB may be associated with outcomes for some who undergo surgery first, but not for those who receive neoadjuvant chemotherapy.

Staging in thick cutaneous malignant melanoma: A sequenced approach

BackgroundPatients with thick cutaneous pT4 malignant melanoma are at high risk for metastatic disease and optimal staging is poorly defined. This study examines the frequency and modality of pre-operative staging to provoke thought on optimal staging. MethodsA retrospective study was performed of patients with clinical T4N0 melanoma diagnosed between 2015-2017. The modality (sentinel lymph node biopsy and/or imaging), timing, and findings of staging investigations were assessed. ResultsOne hundred thirty-six patients with pT4a or pT4b cutaneous melanoma and clinically negative regional lymph nodes were included. Forty patients underwent no staging. Thirty-six patients underwent pre-operative imaging, and of these, regional or distant disease was identified in seven patients (19%). Another 36 patients underwent upfront sentinel lymph node biopsy concurrently with wide local excision. A positive sentinel lymph node biopsy was found in eight (22%) of these patients of which two had regional or distant metastatic disease on post-operative imaging. Of 16 who underwent a sentinel lymph node biopsy after negative pre-operative imaging, three had a positive sentinel lymph node biopsy. ConclusionStaging is non-standardized and underutilized in patients with thick melanoma. With evolving systemic treatment options, a well-defined approach to staging, with consideration for pre-operative imaging in pT4 patients, is essential for high-risk patients.

Sentinel lymph node positivity in melanoma: Which risk prediction tool is most accurate?

BackgroundSentinel lymph node biopsy for melanoma determines treatment and prognostic factors and improves disease-specific survival. To risk-stratify patients for sentinel lymph node biopsy consideration, Memorial Sloan Kettering Cancer Center and Melanoma Institute Australia developed nomograms to predict sentinel lymph node positivity. We aimed to compare the accuracy of these 2 nomograms. MethodsA multi-institutional study of patients with melanoma receiving sentinel lymph node biopsy between September 2018 and December 2022 was performed. The accuracy of the 2 risk prediction tools in determining a positive sentinel lymph node biopsy was analyzed using receiver operating characteristic curves and area under the curve. ResultsIn total, 532 patients underwent sentinel lymph node biopsy for melanoma; 98 (18.4%) had positive sentinel lymph node. Increasing age was inversely related to sentinel lymph node positivity (P < .01); 35.7% of patients ≤30 years had positive sentinel lymph node compared with 9.7% of patients ≥75 years. When we analyzed the entire study population, accuracy of the 2 risk prediction tools was equal (area under the curveMemorial Sloan Kettering Cancer Center: 0.693; area under the curveMIA: 0.699). However, Memorial Sloan Kettering Cancer Center tool was a better predictor in patients aged ≥75 years (area under the curveMemorial Sloan Kettering Cancer Center: 0.801; area under the curveMelanoma Institute Australia: 0.712, P < .01) but Melanoma Institute Australia tool performed better in patients with a higher mitotic index (mitoses/mm2 ≥2; area under the curveMemorial Sloan Kettering Cancer Center: 0.659; area under the curveMelanoma Institute Australia: 0.717, P = .027). Both models were poor predictors of sentinel lymph node positivity in young patients (age ≤30 years; area under the curveMemorial Sloan Kettering Cancer Center: 0.456; area under the curveMelanoma Institute Australia: 0.589, P = .283). ConclusionThe current study suggests that the 2 risk stratification tools differ in their abilities to predict sentinel lymph node positivity in specific populations: Memorial Sloan Kettering Cancer Center tool is a better predictor for older patients, whereas Melanoma Institute Australia tool is more accurate in patients with a higher mitotic index. Both nomograms performed poorly in predicting sentinel lymph node positivity in young patients.

The Use of Sentinel Lymph Node Biopsy in Patients Undergoing Mastectomy for DCIS

BackgroundCurrent guidelines do not recommend routine sentinel node biopsy (SLNB) for ductal carcinoma in situ (DCIS), except in the setting of mastectomy or microinvasive disease. This study aimed to evaluate national SLNB utilization in women undergoing upfront mastectomy for DCIS, identify predictors of SLNB utilization, and determine the percentage with a positive SLNB. MethodsA retrospective cohort analysis was performed using the NCDB of women with clinical DCIS who underwent upfront mastectomy between 2012 and 2017. Demographic and clinicopathologic variables were compared between patients who underwent SLNB and those who did not. Multivariate logistic regression models were used to identify factors associated with SLNB utilization and positive SLNB. ResultsAbout 38,973 patients met inclusion criteria: 34,231 (88%) underwent SLNB and 4742 (12%) had no surgical axillary staging. Most patients were age 50-69 (51%), non-Hispanic White (71%), with private insurance (66%). On multivariate analysis, older patients were less likely to receive SLNB (P < .01), while patients with higher grade DCIS were more likely to undergo SLNB (P < .01). In those who underwent SLNB (n = 34,231), only 1,149 (3.4%) had nodal involvement. Non-Hispanic Black patients had increased odds of a positive SLNB (P < .01), while those with estrogen receptor positive disease were less likely to be node positive (OR 0.68, P < .001). ConclusionsWhile 88% of patients had a SLNB, only 3.4% were found to be node positive. Given this low rate, it is reasonable to consider SLNB omission in select patients with low grade, hormone receptor positive DCIS undergoing upfront mastectomy.

Does Sentinel Lymph Node Biopsy Influence Subsequent Management Decisions in Women With Breast Cancer ≥ 70 Years Old?

BackgroundThere have been ongoing attempts to de-escalate surgical intervention in older breast cancer patients in recent years. However, there remains ongoing hesitancy amongst surgeons to de-implement axillary staging in this cohort. The supporting argument for performing a sentinel lymph node biopsy (SLNB) is that it may guide subsequent management. MethodsA retrospective review was performed of 356 SLNBs, in 342 women ≥ 70 years of age with invasive breast cancer, between 2014 and 2022 in a single institution. Data were collected on patient and tumor characteristics and subsequent management for all patients and for patients with ER+/HER2-, early-stage disease. ResultsPositive SLNB significantly increased likelihood of receiving adjuvant chemotherapy (CTh) in patients aged 70-75 in all clinical subtypes (OR 4.0, 95% CI, 1.6-10; P = .0035). Positive SLNB did not significantly increase likelihood of receiving adjuvant CTh in patients aged 75-80, however, an Oncotype Dx score of ≥ 26 did (OR 34.50, 95% CI, 3.00-455.2; P = .0103). Positive SLNB was significantly associated with receiving adjuvant radiotherapy (RTh) in all patients aged 70-75 (OR 4.5, 95% CI, 2.0-11; P = .0004) and 75-80 (OR 9.7, 95% CI, 2.7-46; P = .0015). In patients aged ≥ 80 years, positive SLNB did not have a significant influence on subsequent treatments. ConclusionIn this study, SLNB did not significantly influence subsequent management decisions in patients over 80 and should rarely be performed in this cohort. However, SLNB still had a role in patients aged 70-80 and should be used selectively in this cohort.

Abstract PO5-23-04: Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study

Abstract Introduction Traditionally, sentinel lymph node biopsy (SLNB) has been used to stage the axilla in early breast cancer (EBC) to guide adjuvant treatment recommendations. Following advances in tumor biology understanding, targeted systemic therapies and genomic testing, with increasing de-escalation of axillary surgery, its role may be less critical especially in selected groups of women. Aims Evaluate clinical utility of SLNB in adjuvant treatment recommendations for women ≥ 70 years with EBC. Methods Retrospective cohort study of women ≥ 70 years with cT1-2N0 EBC undergoing primary surgery and SLNB between 01/2017-12/2022 at The Royal Marsden Hospital (RMH), University Hospital Zurich (USZ) and Seoul National University Hospital (SNUH) in the United Kingdom, Switzerland and South Korea respectively. Simple descriptive statistics and non-parametric tests were performed as appropriate. Results A total of 884 patients were included in the analysis, with 584 patients from RMH, 148 from USZ and 152 from SNUH. The median age was 75 (IQR 72-79) years. Most cancers were invasive ductal (82.9%), grade 2 (61.4%), hormone receptor (HR) positive/HER2 negative (82.9%) with a median tumor size of 17 (IQR 4-50) mm. SLNB was positive in 116 (13.1%) patients. Of these 116 patients, 20 (17.2%) had completion ALND; 7/20 had further RT up to levels 3&amp;4 of the axilla. Of these 116 patients, 96 patients (82.8%) avoided ALND; 25/96 had no further treatment, and 71/96 patients had loco-regional axillary RT (8/71 had RT to levels 1&amp;2 and 63/71 had RT up to levels 3&amp;4). As per international guidelines for patients with EBC with 1-2 positive macrometastases on SLNB treated with breast conserving surgery and breast RT, 5/20 could have been spared ALND, and 50/71 axillary RT. Completion ALND was more likely to be performed at SNUH compared to the other 2 units (p&amp;lt; 0.0001). Axillary RT was more likely to be administered at SNUH and less likely at RMH (p&amp;lt; 0.0001). The multidisciplinary team (MDT) recommended adjuvant chemotherapy (AC) in 146 (16.5%) patients and 100 received it. Of those with a positive SLNB (n=116), AC was recommended in 35, and received by 29. Recommendation for AC was significantly associated with younger age (p=0.021), fewer comorbidities (p=0.003), higher tumor grade (p&amp;lt; 0.0001), increased tumor size (p&amp;lt; 0.0001), HR negative status (p&amp;lt; 0.0001), high genomic risk profile (p&amp;lt; 0.0001) and positive SLNB status (p&amp;lt; 0.0001), but not center (p=0.497). A subgroup analysis of 505 patients with cT1N0, HR+/HER2- EBC, representing a more favorable prognosis group, was performed. Here, 52/505 (10.3%) patients had positive SLNB, of whom 11 had no further axillary treatment, 9 underwent ALND and 32 axillary RT, where 4/9 could have been spared ALND and 28/32 axillary RT as per international guidelines mentioned above. AC was recommended in 26/505 (5.15%) women and 23 received it. AC was not recommended in 39/52 (75%) cases, despite a positive SLNB. MDT recommendation for AC was associated with grade 3 (p&amp;lt; 0.0001), multifocal disease (p=0.021), positive SLNB status (p&amp;lt; 0.0001), high genomic risk profile (p&amp;lt; 0.0001), lower age (p=0.044), fewer co-morbidities (p=0.001) and center (p=0.007) with SNUH being more likely than the other 2, but not ethnicity (p=0.130); AC receipt was associated with the same factors except age (p=0.347). Conclusions Real-world data demonstrates axillary overtreatment despite evidence of the safety of de-escalation of axillary management in EBC. Only a small proportion of women ≥ 70 years with EBC had positive SLNB that may influence adjuvant treatment recommendations, especially with favorable prognosis tumors. In such cases, where clinical morbidity and financial burden of SLNB may outweigh the benefits, a nuanced discussion for opting in SLNB rather than routine performance should be considered. Citation Format: Radhika Merh, Denise Vorburger, Ji-Jung Jung, Han-Byoel Lee, Marios Tasoulis. Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study [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 PO5-23-04.

Abstract PO5-17-12: Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer

Abstract Background: Breast cancer (BC) with low expression of HER2 (HER2-low) might constitute a group of tumors with unique clinical and biological characteristics. Little is known about axillary downstaging and nodal surgical outcomes in HER2-low BC after neoadjuvant chemotherapy (NACT). The aim of this study was to evaluate axillary response and surgical management of the axilla in HER2-low BC patients submitted to NACT. Methods: In this cross-sectional single center study, we consecutively included all patients diagnosed with early HER2-negative BC between 2017 to 2021 that were treated with NACT. Patients must have biopsy-confirmed stage II-III BC, submitted to breast surgery after NACT. Clinical and pathological response in the axilla, type of axillary surgery, and surgical outcomes data were collected. HER2-low was defined by IHC score 1+, or 2+ ISH non-amplified; HER2-zero was defined by IHC score 0. Pathological response was determined locally. Results: At diagnosis, 291 patients had clinically involved axillary nodes (cN1: 69.4%; cN2: 25.1%; cN3: 5.5%). Among 136 patients eligible for SLN biopsy after NACT, 77 (26.5%) had pathologically negative SLN. Of those submitted to upfront axillary dissection (n=154), 52 (33.7%) had pN0 disease. In total, 129 (44.3%) patients with clinically involved axillary lymph nodes at diagnosis were converted to cN0 after NACT. There was no difference in the rate of axillary downstaging between HER2-low and HER2-zero tumors, 17.8% vs 26.5%, respectively (p=0.0026). 236 patients were submitted to sentinel lymph node biopsy (SLN), of whom 214 (81.4%) with blue dye-only, 40 (15.2%) with radioactive isotope, and 7 (2.7%) with dual tracer. SLN detection failure were reported for 12 patients (0.046%). Mean number of lymph nodes retrieved were 2.7. Most patients had a negative SLN biopsy (180/263; 68.4%), of whom 91 (50.6%) were HER2-low and 89 (49.4%) were HER2-zero. Positive SLN biopsy were reported in 83 patients (isolated tumor cells: 20,5%; micrometastasis: 24.1%; macrometastasis: 55.4%), with capsular extravasation in 25.3%. A positive SLN biopsy occurred in 61.4% of patients with HER2-low tumors, and in 38.5% of patients with HER2-zero tumors. Among patients with a positive SLN biopsy (n=83), 67 were submitted to axillary dissection, of whom 39 (58.2%) had no additional nodes involved (HER2-low: 61.5%; HER2-zero: 38.4%). Considering N0 tumors at diagnosis, 127 patients were submitted to SNL, and only 18.9% had a positive result (HER2-low: 66.6%; HER2-zero: 33.3%). In the subgroup of initially cN+ disease, 136 (46.7%) underwent SLN biopsy, with 59 (43.4%) with a positive result (HER2-low: 59.3%; HER2-zero: 40.7%). Conclusions: Our results showed that HER2-low BC patients had a statistically significant lower frequency of axillary downstaging after NACT. More than 40% of patients with cN+ at diagnosis were downstaged to cN0 and were submitted to SNL biopsy. Axillary dissection were avoided in roughly 25% of patients with cN+ BC at initial staging. Citation Format: Leonardo Roberto da Silva, Guilherme Sartori, Susana Ramalho, Tomás Reinert, Mahira Lopes Da Rosa, Grazielle Morais Tavares, Higor Mantovani, Vivian Vasconcelos, Ana Elisa Ribeiro Da Silva Cabello, Guilherme Coelho, Jovana Mandelli, Facundo Zaffaroni, Carlos Barrios, Marcia Silveira Graudenz, César Cabello. Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer [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 PO5-17-12.

Abstract PO3-23-07: Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients

Abstract Background: Axillary surgery is now routinely de-escalated in clinically node negative breast cancer patients with limited axillary nodal burden (up to 2 involved sentinel nodes) based on the results of ACOSOG-Z0011 and AMAROS trials. However, patients with proven axillary metastasis following on ultrasound (AUS) guided core needle biopsy (CNB), undergoing primary surgery are still subjected to an axillary lymph node dissection (ALND) irrespective of the magnitude of the axillary nodal burden. If we could predict axillary nodal burden with a low false negative rate (FNR) for the presence of extensive axillary nodal involvement, we can then hypothesize that axillary surgery could be safely de-escalated in this cohort of patients. We investigated whether pre-operative AUS suggesting limited axillary burden is sensitive enough to rule out gross axillary disease burden. Methods: A single institution retrospective study. We undertook an electronic chart review of all T1 to T3 patients undergoing upfront ALND with either mastectomy or breast conserving surgery between January 2019 and June 2023. Patients with palpable axillary nodes, locally advanced breast cancer or a completion ALND after positive sentinel lymph node biopsy (SLNB) were excluded from the study. Clinical and pathological characteristics associated with nodal burden of disease were evaluated. Limited axillary burden was defined as &amp;lt; 2 involved nodes with ≥3 taken as gross nodal burden for primary analyses. Sensitivity analyses were carried out with limited axillary burden defined as &amp;lt; 3 involved nodes (N1) and ≥4 (N2) taken as gross nodal burden. Subgroup analyses in T1 or T2 tumors were carried out as well. The probabilities of discordant events, defined as limited burden on AUS-CNB but gross burden on final histopathology evaluation (HPE), assuming 10% FNR, were estimated using inverse cumulative binomial distribution function. Results: Data on the exact number of suspicious nodes on AUS were missing for 2 patients, therefore, the final study cohort included 39 patients. The correlation between AUS nodal burden and that on HPE was moderate (Spearman’s rho = 0.48; p = 0.0018). The sensitivity and specificity of AUS in identifying gross nodal burden were 61% and 81% respectively. Observation of 9 discordant events in 22 patients with low burden on AUS ruled out an FNR of &amp;lt; 10% with 99.99% certainty. The sensitivity and specificity in T1/T2 subgroup were 60% and 75% respectively. The sensitivity analyses classifying N1 as limited and N2 as gross axillary burden showed the sensitivity and specificity of 35% and 82% respectively and an FNR of &amp;lt; 10% was ruled out with 99.996% certainty. Conclusion: Pre-operative AUS alone lacks the sensitivity and specificity to accurately predict the true axillary nodal burden to safely guide de-escalation of axillary surgery. AUS followed by targeted axillary dissection (TAD) in conjunction with a dual technique SLNB may provide the desired sensitivity and specificity to guide de-escalation of axillary surgery. A prospective evaluation of this approach is merited. Given the limited number of patients that could be enrolled in such prospective study from individual institutions, an international collaborative effort is needed to address this important research question. Citation Format: Nidhi Garg, Mangesh Thorat, Hisham Hamed, Ashutosh Kothari. Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients [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 PO3-23-07.

Abstract PO3-02-08: Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China

Abstract Objective: The management of positive sentinel lymph node biopsies (SLNB) in patients with early-stage breast cancer remains a matter of controversy. Some studies have shown that not all breast cancer patients with positive sentinel lymph nodes (SLNs) benefit from further axillary lymph node dissection (ALND). Our study aims to analyse the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis in Chinese early-stage breast cancer patients with positive sentinel lymph nodes. Methods: The clinical data of 708 patients with early-stage breast cancer who attended The Fourth Hospital of Hebei Medical University for surgical treatment from January 2016 to December 2021 was retrospectively analyzed. All of them were female breast cancer patients with positive sentinel lymph nodes and underwent ALND. The patients were divided into modeling group and validation group according to the time of treatment. The patients in the modeling group were divided into a positive NSLN group and a negative NSLN group. The characteristics: age, maximum tumor diameter, the number of positive SLNs, proportion of positive SLNs, vessel carcinoma embolus, nerve invasion, status of ER, PR, HER-2 and Ki-67 were included in the analysis. And the independent risk factors of NSLN metastasis were screened by univariate (chi-square test) and multivariate (logistic regression) analysis. A nomogram model was established according to the screened independent risk factors, and the model was externally validated by the validation group. The ROC curve was plotted to calculate the area under the curve (AUC) and evaluate the predictive power of the nomogram model. A calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: Among the 708 patients, (modeling group n=410, validation group n=298), the average age, average number of positive SLNs, and NSLN positive rate were 50.9±11.1, 1.55±0.87 and 25.71%. The univariate analysis revealed statistically significant differences in the number of positive SLNs (P&amp;lt; 0.001), the proportion of positive SLNs (P &amp;lt; 0.001), vessel carcinoma embolus (P=0.001), nerve invasion (P=0.012), and ER status (P=0.029) in the NSLN-positive group compared with the negative group. The multifactorial logistic regression analysis revealed that the number of positive SLN (P=0.002; OR: 1.700; 95% CI: 1.219-2.370), the proportion of positive SLN (P=0.048; OR: 3.214; 95% CI: 1.001-10.490), vessel carcinoma embolus (P=0.010; OR: 2.076; 95% CI: 1.194-3.612), nerve invasion (P=0.024; OR: 2.119; 95% CI: 1.221-3.678), and ER status (P=0.045; OR: 2.978; 95% CI: 1.022-8.675) were independent risk factors for NSLN positivity. Furthermore, the nomogram was built using these 5 factors and validated on 298 patients in the validation group. The AUC was 0.728 (P&amp;lt; 0.001; 95%CI: 0.673-0.784) in the modeling group and 0.810 (P&amp;lt;0.001; 95%CI: 0.735-0.886) in the validation group. The calibration curves of the modeling and validation groups were close to the ideal curve, and DCA also showed that the model could be applied in clinical practice. Conclusion: For early-stage breast cancer with positive SLNs, these factors as the positive number of SLNs &amp;gt; 2, the ratio of positive SLNs &amp;gt; 50%, vessel carcinoma embolus, nerve invasion and ER-positive could predict NSLN metastasis well. The proposed nomogram appears to accurately estimate the likelihood of positive NSLNs and may greatly help the surgeon to decide intraoperatively whether to perform further ALND and avoid non-essential ALND as well as postoperative complications. Citation Format: Zhenchuan Song, Xueyi Zhao, Liu Yang. Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China [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 PO3-02-08.

Abstract PO4-16-10: Overall survival in sentinel node biopsy and axillary dissection: a real-world data

Abstract Background: Information about the status of the axilla (presence or absence of lymph node disease) is important for breast cancer (BC) treatment decision-making. Axillary dissection (AD) has been gradually substituted by sentinel node biopsy (SLNB) in clinical node negative patients and intraoperative evaluation became a routine. Most of the patients with a positive node in an intraoperative evaluation were submitted to AD, and when a negative intraoperative evaluation but a positive paraffin evaluation was found a new axillary surgery was a routine. Both approaches were gradually abandoned with the publication of the ACOSOG Z011 study showing no difference in local recurrence or overall survival (OS). Objective: To evaluate the number of patients with BC who meet the criteria of Z011 trial and could be spared of AD and compare the outcomes of the SLNB only and those that had AD. Methods: Patients with BC that were submitted to upfront surgery and had at least one positive node in SLNB were included in these retrospective analyses at Pérola Byington Hospital database, diagnosed between 1992 and 2019. Clinical and pathological characteristics were extracted from the database and patient medical records. T-test or chi-square test was used to individually analyze the association of each variable between the groups. Multivariate analysis was used to calculate odds ratio (OR) and 95% confidence intervals (CI) for independent variables correlated with positive AD. Cox regression was used for survival analysis, and survival curves were plotted using the Kaplan-Meier method, analyzing the difference between curves using the Log-rank test. R software version 4.1.1 was used for all analyses, with a p-value &amp;lt; 0.05 considered statistically significant. Results: A total of 729 patients were analyzed, with a mean age of 54.1 (±11.6) years at diagnosis. Most patients (n=633, 86.8%) underwent AD after a positive SLNB and 40,3% of the patients that were submitted to AD the only positive node was the sentinel node. After AD, 63,3% of these patients had 1 or 2 lymph nodes positive and met the Z011 criteria trial. The mean number of lymph node in AD was 12.2. Most patients (72.7%) were diagnosed at clinical stage II, 62% had nuclear grade 2 tumors, 52.9% had Luminal B subtype, and 63% were postmenopausal. Furthermore, 58.5% of patients underwent breast-conserving surgery, and 5.2% of patients experienced recurrence. The chance of AD was observed 2,2 times for the luminal B (OR 2.163, 95% CI 1.104-4.239, p=0.025), 2,1 times HER2-positive with receptor positive (OR 2.125, 95% CI 1.160-3.893, p=0.015), and 2,8 times for triple-negative (OR 2.806, 95% CI 1.013-7.757, p=0.047) compared to Luminal A. Patients that were submitted to AD had worse outcome when compared to SLNB, the overall survival showed a 94.4% higher risk of death with a median survival of 11 years (HR 1.944, 95% CI 1.20-3.14, p=0.006). Conclusion: These retrospective analyses showed 63,3% of the patients that had a positive node in a SLNB could be spared from AD (based on Z011 trial). Patients submitted to AD had worse outcome and these findings needs to be clarified. Citation Format: Renata Pares, Andre Mattar, Juliana de Lima, Marcelo Antonini, Francisco Pimentel Cavalcante, Luiz Henrique Gebrim. Overall survival in sentinel node biopsy and axillary dissection: a real-world data [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 PO4-16-10.

Abstract GS02-06: Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial

Abstract Background The omission of a completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy in patients with clinically node-negative breast cancer has been demonstrated to yield survival outcomes non-inferior to routine cALND in breast-conserving surgery followed by whole-breast irradiation (ACOSOG Z0011 and IBCSG 23-01 trials), and to axillary radiotherapy (RT) regardless of breast surgery (EORTC AMAROS trial). Mainly due to the under-representation of mastectomy patients, and a limited number of observed events compromising statistical power, the international randomized SENOMAC trial was initiated in 2015. The main aim of this non-inferiority trial was to address knowledge gaps relating to individuals treated by mastectomy, those with larger tumors and those with SLN extracapsular extension. Method The SENOMAC trial (NCT 02240472) enrolled patients with cT1-3cN0 primary breast cancer and 1-2 SLN macrometastases at 67 sites in five countries between January 27, 2015, and December 31, 2021. Participants were randomized 1:1 between cALND (standard) and omission of cALND (intervention). Stratification was per country. Breast-conserving surgery and mastectomy were eligible surgical interventions. Preoperative axillary ultrasound was mandatory; patients with non-palpable suspicious axillary lymph nodes, even if proven metastatic by biopsy, were eligible. SLN extracapsular extension was allowed. Adjuvant radiotherapy was dictated by national guidelines and not by the trial protocol. Statistical sample size calculation was based on the primary outcome overall survival. Non-inferiority was defined as a 5-year overall survival not worsened by more than 2.5% when refraining from cALND after the observation of 190 all-cause deaths in a target sample size of 3000 included patients. In the present analysis, the pre-specified secondary outcome of recurrence-free survival is reported. Results Out of 2766 randomized individuals, 2539 comprised the per-protocol population: 1204 in the standard and 1335 in the intervention group. Median follow-up was 37.1 months (1.5-75.0) and median age at inclusion 61 years (range 20-94). Most tumors belonged to the luminal subtype (93.6%); tumor stage was T1 in 1358 (53.5%), T2 in 1034 (40.7%) and T3 in 146 participants (5.8%). Out of 347 participants with suspicious lymph nodes on ultrasound, 36 had confirmed non-palpable metastasis. SLN extracapsular extension was reported in 866 (34.1%). The breast was conserved in 1621 (63.8%) and a mastectomy performed in 918 (36.2%) patients. Most patients (2127, 83.8%) received radiotherapy including nodal target volumes. In 34.1% of the standard group, additional non-SLN metastases were identified on cALND. Overall, 104 recurrences were reported, 54 (4.5%) in the standard and 50 (3.7%) in the intervention group. Of these, 11 recurrences were found in the ipsilateral axilla: 5 (0.4%) and 6 (0.5%), respectively. Recurrence-free survival did not differ between groups (country-adjusted HR 0.89, 95% CI 0.65-1.20). Conclusion Despite extended inclusion criteria, there was no difference in recurrence-free survival whether cALND was omitted (intervention) or not (standard). Patients undergoing mastectomy will specifically be addressed in subgroup analyses. Long-term follow-up is crucial considering the high proportion of luminal cancers. Citation Format: Jana de Boniface, Tove Tvedskov, Bergkvist Leif, Jan Frisell, Yvette Andersson, Sara Alkner, Malin Sund, Roger Olofsson Bagge, Dan Lundstedt, Oreste Davide Gentilini, Michalis Kontos, Toralf Reimer, Birgitte Offersen, Thorsten Kühn, Lisa Rydén, Peer Christiansen. Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial [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 GS02-06.

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

Clinical and Surgical Evaluation of Sentinel Node Biopsy in Patients with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

The medical and surgical treatment of endometrial cancer (EC) is evolving toward a more patient-centered and personalized approach. The role of laparoscopic sentinel node biopsy (SNB) for early-stage EC is unclear, and very few data are available for atypical endometrial hyperplasia (AEH). The present study investigated the effectiveness of SNB combined with laparoscopic hysterectomy in patients with early-stage EC and AEH. This was a retrospective, single-center cohort study for the period from January 2018 to December 2023. A total of 102 patients with atypical hyperplasia (n=20) and early-stage EC (n=82) findings on diagnostic curettage underwent pelvic sentinel node biopsy during the final operation. Eleven patients (55%) who had initially been diagnosed with AEH were found to have EC in the final pathology report. No lymph node metastases were detected in patients who had initially been diagnosed with AEH; a 3.6% rate of positive SNBs was found in patients with EC. Changes in tumor grade occurred in 31.3% of the patients and changes in FIGO stage in 33%. Bilateral sentinel node (SN) mapping was successful in 94.1% of the patients. The postoperative outcomes were comparable to those of routine clinical practice without SNB. SNB can be safely offered to patients who have precursor lesions and early-stage EC without notably extending surgical times or increasing postoperative morbidity. This approach can be considered and is safe for patients diagnosed with AEH, but it appears to have a rather small impact on these patients.

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.