Subsequent Axillary Lymph Node Dissection Research Articles

Abstract PO3-22-07: Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used for axillary downstaging in clinically node-positive breast cancer patients, and a considerable proportion achieves axillary pathological complete response (ax-pCR). After NACT, axillary staging can be done by targeted axillary dissection (TAD). In case of metastases at TAD, axillary lymph node dissection (ALND) is offered regardless of metastases size. This contrasts primary surgery, where small sentinel node metastases (ypN0(i) and ypN1mi) and ≤2 positive sentinel nodes do not confer ALND, although a proportion of patients with small metastases have additional metastatic lymph nodes (LNs) in the axilla. So far, the residual metastatic burden in the axilla when TAD LNs are positive after NACT is unknown. If subgroups of patients with low residual metastatic burden in the axilla (non-TAD LNs) could be identified, these subgroups may be offered de-escalated axillary treatment. Therefore, we investigated the risk of residual metastatic burden in the axilla when the TAD LNs harbored metastases. Methods: We retrospectively retrieved DBCG data on patients staged by TAD after NACT in Denmark between 1.1.2016-31.8.2021. We registered: age, breast biopsy date, type of surgery, type of axillary surgery, count of LNs, sentinel nodes, and marked lymph nodes with and without metastases, including metastasis size, breast tumor histology and receptor subtype, breast tumor size at diagnosis and in the surgical specimen, malignancy grade and type of neoadjuvant treatment. We excluded patients with inflammatory breast cancer, < 4/>8 cycles of NACT, or a non-standard NACT regimen. The primary outcome was risk factors for having high ( >3), low (1-3), or no residual metastatic burden in the axilla when the TAD LNs harbored metastases. We modeled risk factors for both high and low residual metastatic burden in the axilla using multivariable logistic regression and constructed risk models based on the regression coefficients. Results: We identified 1626 patients receiving NACT and TAD in the inclusion period. After excluding ineligible patients and patients who achieved ax-pCR with no subsequent ALND (46%), the study included 383 patients with positive LNs at TAD for further analysis: thereof 188, 127, and 68 with 0, 1-3 and >3 positive non-TAD LNs, respectively. In the adjusted logistic regression analysis, we found that breast pCR (OR= 0.06, 95% CI < .01-0.41, p < .001) and a low proportion of positive TAD LNs (0-66% vs >66%) (OR=0.32, 95% CI 0.17-0.58, p = < .001) were associated with low risk of high residual metastatic burden in the axilla. Patients with one or both low-risk factors present had an 8% (14 of 176 patients) risk of high residual metastatic burden in the axilla. The predictive value of the model for having < 3 non-TAD LN metastases was 92%. When analyzing the 315 patients with ≤3 positive non-TAD LNs, the adjusted logistic regression analysis of 1-3 vs 0 positive non-TAD LNs showed that ypN0(i) in the TAD LN (OR=0.14, 95% CI 0.04-0.53, p = 0.002), small tumor size at diagnosis (20-49 mm vs ≥ 50 mm) (OR = 0.29, 95% CI 0.14-0.60, p = 0.002), breast pCR (OR= 0.38, 95% CI 0.15-0.98, p = 0.04) and low proportion of positive TAD LNs (33-66% vs >66%) (OR= 0.46, 95% CI 0.27-0.77, p = 0.01) were associated with no residual metastases in the axilla. Using these risk factors, 19% (11/58) of the patients in the lowest risk quartile had further metastatic spread to the axilla. Conclusion: Based on an extensive breast cancer registry, we find that breast pCR, low proportion of positive TAD LNs, small metastases, and small tumor size are associated with low risk of residual metastatic LNs in the axilla when the TAD LNs are positive after NACT. With these risk factors, we propose two models to identify patients with low non-TAD residual metastatic burden and patients with a high likelihood of no further metastases. The models can guide breast surgeons in de-escalating axillary treatment in these groups. Citation Format: Frederikke Munck, Maj-Britt Jensen, Ilse Vejborg, Maria Gerlach, Maja Maraldo, Niels Kroman, Tove Tvedskov. Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment [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 PO3-22-07.

Single-Fraction Pre-Operative Stereotactic Radiosurgery for Early-Stage Breast Cancer: Pathological Findings

to assess pathological results after single-fraction pre-operative stereotactic radiosurgery of early-stage breast cancer. A phase 2 clinical trial to investigate the feasibility of pre-operative radiosurgery for early-stage breast cancer was conducted. Eligible patients are women older than 50 years, with histologically proven breast invasive ductal carcinoma, hormonal receptors positive/human epidermal grow factor receptor 2 negative, any grade, tumor size < 3cm, unifocal, with no nodal involvement, and suitable for breast conservative surgery. An expert radiologist injected ultrasound-guided a fiducial marker to precisely identify tumor positioning. The Planning Target Volume (PTV) is created by adding a 3mm margin to the Gross Tumor Volume (GTV). A single fraction of 30-33 Gy is delivered to 95% of PTV. Patients had a breast MRI scan 6-12 weeks after treatment to evaluate the rate of radiological response. Surgery was performed at 9 to 16 weeks after irradiation. From January 2022 to December 2022, 33 patients underwent single-fraction radiosurgery, of whom 29 had breast conserving surgery (BCS). BCS was performed at 9-10 weeks for the first 14 patients, at 14-16 weeks for 13 patients, and at 18-19 weeks for 2 patients. The pathological response was defined as complete response (pCR) if no residual tumor cells were found, partial response (pPR), or no response. The pPR were also subdivided into 3 subgroups according to the rate of residual disease: < 10%, 10-50%, and > 50%. Two patients (7%) achieved pCR, both treated with 33 Gy and operated at 14 weeks. Twenty-five patients (86%) had pPR, of which 7 patients (24%) had residual disease < 10%, 9 patients (31%) between 10-50% and 9 patients (31%) over 50%. Two patients (7%) had no pathological response. All patients had sentinel lymph node biopsy at the time of surgery. Positive micrometastatic nodal involvement was found in 3 patients (11%), of which 2 patients (7%) had macrometastases (pN1a) and received subsequent axillary lymph node dissection. All patients had negative surgical margins. Not any acute and sub-acute surgical complications were observed. Single-fraction pre-operative stereotactic radiosurgery for early-stage breast cancer leads to a high rate of complete or partial pathological response with surgery performed at 2-4 months following irradiation.

Abstract P2-14-21: NiToNo Study. Evaluation in terms of quality of life and upper extremity functionality after Targeted Axillary Dissection versus lymphadenectomy

Abstract Introduction: Targeted Axillary Dissection (TAD) is the combination of the sentinel lymph node biopsy (SLNB) and retrieval of the clipped node that was proved positive before neoadjuvant treatment (NAT). Previous studies have demonstrated that this approach has a low false-negative rate in patients with cN+ before NAT. Current guidelines recommend axillary radiotherapy in cN+ despite a complete pathological response reported after NAT. Aim: To evaluate if TAD improves the quality of life and arm functionality compared to axillary lymph node dissection (ALND) in patients with cN+ before NAT. Methods: Prospective observational study. The study started in 2017 and ended in 2021. We included patients with one to three suspected lymph nodes and at least one confirmed by fine-needle aspiration. Suspicious lymph nodes were clipped before NAT. After NAT if a complete radiological response was achieved by axillary ultrasound, TAD was performed. During surgery, we used ultrasound-guided marked lymph node dissection and dual tracer SLNB. Clipped and SLN were assessed with intraoperative frozen section H&amp;E, standard H&amp;E, and IHC with CKAE1/AE3. After surgery, the breast tumor board analyzes the pathological findings and the surgical performance. When ITC, micro-metastases, or macro-metastases were found in the nodes, or when surgical performance is considered suboptimal, we proceed to ALND. We assessed QoL with standard forms and upper extremity mobility and lymphedema by physical examination. Results: We analyzed 44 women. Median age 53.9 years old. ALND was performed on 28 patients and TAD on 16 patients. Age and other confounding factors such as (BMI, type of surgery, and type of NAT) were similar in both groups. Median follow-up time: 24 months (5-60). No regional relapse in both groups. The axillary staging is shown in table 1. The surgical procedure and indications for ALND are shown in Table 2. Any patient with a Luminal-A-like profile had an axillary response to NAT and subsequent ALND was performed in all 4 patients. By contrast, patients with HER2 overexpression or triple negatives had better axillary responsiveness and 12/21 were stratified only with TAD. Two patients had a false positive finding on the post-NAT axillary ultrasound (one patient with LuminalB-Her2 positive tumor and one patient with HER2 positive not luminal) and ALND was performed, complete pathological response with only fibrosis was observed. Indications of ALND are shown in table 1. On the questionnaires, health status perception (84.9 TAD vs 65.77 ALND, p=0.02), QoL (83.33 TAD vs 64.29 ALND p=0.03), upped extremity symptoms (8.33% TAD vs 30.16% ALND, p&amp;lt; 0.01) and breast symptoms (14.06% TAD vs 31.25% ALND, p=0.03) are better on TAD than in ALND patients. On physical examination, 11 patients of the ALND group had some alteration in functionality (8 patients had limitation of abduction and 7 patients had lymphedema). By contrast, any alteration was found in the patients staged only with TAD. Conclusions: Targeted axillary dissection reduces posttreatment symptomatology and allows a better quality of life with no axillary relapses though follow-up is short. Patients with Luminal-A-like cancer probably are not good candidates for TAD because of a lack of responsiveness and perhaps another approach must be considered. Table 1: Axillary staging after NAT Table 2: Surgical procedure and indications for lymphadennectomy Citation Format: Laia Vila Homs, MAria Lourdes Carrillo-Guivernau, Catalina Sampol, Gabriel Matheu Capo, Pau CAMARASA, Catalina Serra, Monica Mariño, Angela Tarongí, Octavi Cordoba, Antonia Perelló. NiToNo Study. Evaluation in terms of quality of life and upper extremity functionality after Targeted Axillary Dissection versus lymphadenectomy [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 P2-14-21.

Intraoperative predictive model for the detection of metastasis in non-sentinel axillary lymph nodes

Background: To design a software-applied predictive model relating patients clinical and pathological traits associated with sentinel lymph-node total tumor load to individually establish the need to perform an axillary lymph-node dissection. Methods: Retrospective observational study including 127 patients with breast cancer in which a sentinel lymph-node biopsy was performed with the one step nucleic acid amplification method and a subsequent axillary lymph-node dissection. We created various binary multivariate logistic regression models using non-automated methods to predict the presence of metastasis in non-sentinel lymph-nodes, including Log total tumor load, immunohistochemistry, multicentricity and progesterone receptors. These parameters were progressively added according to the simplicity of their evaluation and their predictive value to detect metastasis in non-sentinel lymph-nodes. Results: The final model was selected for having maximum discriminatory capability, good calibration, along with parsimony and interpretability. The binary logistic regression model chosen was the one which identified the variables Log total tumor load, immunohistochemistry, multicentricity and progesterone receptors as predictors of metastasis in non-sentinel lymph-nodes. Harrell’s C-index obtained from the area under the curve of the predicted probabilities by Model 4 was 0.77 (95% CI, 0.689–0.85; p &lt; 0.0005). Conclusions: the combination of total tumor load, immunohistochemistry, multicentricity and progesterone receptors can predict 77% of patients with metastasis in non-sentinel lymph-nodes and said prediction may be made intraoperatively in a feasible manner.

Adding carbon nanoparticles to dual-tracers for the sentinel node evaluation after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers: The TT-SLNB trial.

566 Background: This study measures the feasibility and accuracy of sentinel lymph node biopsy (SLNB) with triple-tracers (TT-SLNB) which combines carbon nanoparticles (CNS) with dual tracers of radioisotope and blue dye, hoping to achieve an optimized method of SLNB after neoadjuvant chemotherapy (NAC) in ycN0 breast cancer patients with pretreatment positive axillary lymph nodes. Methods: Clinically node-negative invasive breast cancer patients with pre-NAC positive axillary lymph nodes who received surgeries from November 2020 to January 2021 were included. CNS was injected at the peritumoral site the day before surgery. Standard dual-tracer (SD)-SLNs were defined as blue-colored and/or hot nodes, and TT-SLNs were defined as lymph nodes detected by any of hot, blue-stained, black-stained, and/or palpated SLNs. All patients received subsequent axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were calculated. Results: Seventy-six of 121 (62.8%) breast cancer patients converted to cN0 after NAC and received TT-SLNB. After NAC, 28.95% (22/76) achieved overall (breast and axilla) pCR. The DR was 94.74% (72/76), 88.16% (67/76) and 96.05% (73/76) for SLNB with single-tracer of CNS (CNS-SLNB), SD-SLNB, and TT-SLNB, respectively. The FNR was 22.86% (8/35) for CNS-SLNB and 10% (3/30) for SD-SLNB. The FNR of TT-SLNB was 5.71% (2/35), which was significantly lower than those of CNS-SLNB and SD-SLNB. The NPV and accuracy was 95.0% and 97.3% for TT-SLNB, respectively. Moreover, a significant relation was seen between the pretreatment clinical T classification and the DR of TT-SLNB (Fisher’s exact test, p= 0.010). Conclusions: TT-SLNB revealed ideal performance in post-NAC ycN0 patients with pretreatment node-positive breast cancers. The application of TT-SLNB reached a better balance between more accurate axillary evaluation and less intervention. Clinical trial information: ChiCTR2000039814. [Table: see text]

Disparities of Management of the Axilla in Women With Clinically Node Negative Breast Cancer

BackgroundIn women with clinically node-negative breast cancer, sentinel lymph node biopsy is the first step in axillary staging. A randomized trial published in 2013 concluded that patients with sentinel lymph node micrometastases (N1mi) do not benefit from axillary lymph node dissection (ALND). We hypothesized that disparities exist in management of the axilla in node-negative patients. MethodsWe included women aged >40 years with nonmetastatic, clinically node-negative breast cancer from 2014 to 2016 in the National Cancer Database. Women treated neoadjuvantly, with large tumors (cT4), or no tumor (cT0) were excluded. Multivariable logistic regression identified patient and facility characteristics associated with undergoing ALND as first axillary surgery and completion ALND in the setting of N1mi disease. ResultsOf 273,951 patients, 22,898 (8%) underwent ALND first. These patients were more likely to be Hispanic (OR: 1.21, 95% CI: 1.10, 1.32), have Medicare (OR: 1.13, 95% CI: 1.03, 1.24), be uninsured (OR: 1.28, 95% CI: 1.08, 1.53), have lower educational attainment (OR: 1.24, 95% CI: 1.17, 1.32), be treated at a community hospital (OR: 1.62, 95% CI: 1.52, 1.74), or reside in the South (OR: 1.19, 95% CI: 1.12, 1.26). In the sentinel lymph node biopsy first group, 8,882 (4%) were classified as N1mi and 1,872 (21%) underwent subsequent ALND. These patients were more likely to be Hispanic (OR: 1.70, 95% CI: 1.19, 2.42) and have the lowest income (OR: 1.62, 95% CI: 1.15, 2.27). ConclusionDisparities persist in implementation of evidence-based management of the axilla in women with clinically node-negative breast cancer.

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Disparities in the Use of Sentinel Lymph Node Dissection for Early Stage Breast Cancer

BackgroundClinical trials have long established the long-term safety of omitting axillary lymph node dissection (ALND) after sentinel lymph node dissection (SLND) in patients with clinically node-negative early stage breast cancer. The variations in utilization of SLND and ALND in this patient population, however, are currently unknown. MethodsAdult female patients (40 years and older) within the National Cancer Database diagnosed with breast cancer between January 2013 and December 2015, who had clinical T1-T2 and N0 disease, and who underwent either SLND (with or without subsequent ALND) or ALND were included. Differences in utilization across race, ethnicity, insurance type, facility, and residential characteristics were assessed using multivariable logistic regression. ResultsOverall, 271,689 patients were included, of which 26,527 (10%) received ALND and 245,162 (90%) underwent SLND. After adjusting for demographics and cancer characteristics, black (odds ratio [OR], 1.11; 95% confidence interval [95% CI], 1.06-1.17) and Hispanic women (OR, 1.16; 95% CI, 1.10-1.24) were more likely to receive ALND. Patients without health insurance (OR, 1.33; 95% CI, 1.19-1.47), compared with private health insurance, and those receiving treatment at community cancer centers (OR, 1.60; 95% CI, 1.53-1.67), compared with academic/research centers, were also more likely to receive ALND. ConclusionsAlthough the vast majority of women undergo SLND, significant disparities exist in its utilization for early stage breast cancer, with traditionally underserved patients receiving unwarranted extensive axillary surgery. Increased patient and surgeon education is needed to decrease variations in care that can affect patient's quality of life.

Third Line Eribulin for Triple-negative Metastatic Breast Ductal Carcinoma Resulting in Extended Progression-free Survival of 57 Months

Eribulin is a non-taxane microtubule inhibitor approved for the treatment of metastatic breast carcinoma after two prior chemotherapeutic regimens. We report a patient with extended progression-free survival (PFS) of more than 57 months with metastatic breast carcinoma treated with eribulin in the third-line setting. A 48-year-old lady was diagnosed with stage IIA (pT2N0M0), high grade, triple-negative, invasive ductal carcinoma (IDC) of the left breast on core needle biopsy. She underwent neoadjuvant chemotherapy with adriamycin, and cyclophosphamide followed by a negative sentinel lymph node (SLN) biopsy. Subsequent mastectomy and axillary lymph node dissection revealed a 2.5 cm, high grade, triple-negative IDC with three additional lymph nodes negative for metastatic carcinoma, consistent with the initial diagnosis. Eight months into the surveillance program, the patient developed a 2.8 cm right lower lobe (RLL) lung mass with standard uptake value (SUV) of 27 on positron emission tomography-computed tomography (PET/CT). Core needle biopsy of the lung lesion revealed sheets of poorly differentiated carcinoma, immunophenotypically compatible with the initial diagnosis of breast pathology. She then commenced single-agent paclitaxel in the 1st line metastatic setting with a significant decrease in RLL lung mass to less than 1 cm with an SUV of 1.7 noted. The patient developed progression after seven months and started 2nd line gemcitabine noting initial improvement and subsequent stable disease for a period of 12 months. Eventual progression of RLL lung nodule measuring 2.1 cm with SUV of 10 noted. Initiated 3rd line eribulin with a notable response on imaging studies within three months and with no evidence of disease (NED) on scans over the subsequent 57 months. Eribulin related mild neuropathy superimposed on previous paclitaxel associated grade 2 neuropathy required a 20% eribulin dose reduction. The patient is currently clinically and radiographically stable with plateaued serum tumor markers. Our patient has shown excellent response and tolerance to eribulin with PFS of over 57 months (nineteen times the norm) which is rare.

Diagnostic performance of axillary ultrasound and standard breast MRI for differentiation between limited and advanced axillary nodal disease in clinically node-positive breast cancer patients

Preoperative differentiation between limited (pN1; 1–3 axillary metastases) and advanced (pN2–3; ≥4 axillary metastases) nodal disease can provide relevant information regarding surgical planning and guiding adjuvant radiation therapy. The aim was to evaluate the diagnostic performance of preoperative axillary ultrasound (US) and breast MRI for differentiation between pN1 and pN2–3 in clinically node-positive breast cancer. A total of 49 patients were included with axillary metastasis confirmed by US-guided tissue sampling. All had undergone breast MRI between 2008–2014 and subsequent axillary lymph node dissection. Unenhanced T2-weighted MRI exams were reviewed by two radiologists independently. Each lymph node on the MRI exams was scored using a confidence scale (0–4) and compared with histopathology. Diagnostic performance parameters were calculated for differentiation between pN1 and pN2–3. Interobserver agreement was determined using Cohen’s kappa coefficient. At final histopathology, 67.3% (33/49) and 32.7% (16/49) of patients were pN1 and pN2–3, respectively. Breast MRI was comparable to US in terms of accuracy (MRI reader 1 vs US, 71.4% vs 69.4%, p = 0.99; MRI reader 2 vs US, 73.5% vs 69.4%, p = 0.77). In the case of 1–3 suspicious lymph nodes, pN2–3 was observed in 30.4% on US (positive predictive value (PPV) 69.6%) and in 22.2–24.3% on MRI (PPV 75.7–77.8%). In the case of ≥4 suspicious lymph nodes, pN1 was observed in 33.3% on US (negative predictive value (NPV) 66.7%) and in 38.5–41.7% on MRI (NPV 58.3–61.5%). Interobserver agreement was considered good (k = 0.73). In clinically node-positive patients, the diagnostic performance of axillary US and breast MRI is comparable and limited for accurate differentiation between pN1 and pN2–3. Therefore, there seems no added clinical value of preoperative breast MRI regarding nodal staging in patients with positive axillary US.

The clinical significance of metastatic breast carcinoma to intramammary lymph node.

The incidence of involved intramammary lymph node (intra-MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra-MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T-stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow-up. Stage 4 cases and/or neo-adjuvant treated patients were excluded. AJCC TN-stage was calculated twice, with and without intra-MLN. Five-year overall survival (OS) and relapse (local and/or distant)-free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra-MLN, TN-stage correlated with OS (P=.016) but not with RFS (P=.19). However, when intra-MLN was included, TN-stage correlated with both OS (P<.001) and RFS (P=.016). In the multivariate analysis, when intra-MLN was excluded, only radiation therapy (RT) correlated with RFS (HR=0.19, 95% CI: 0.054-0.66, P=.009). However, when intra-MLN was included in the TN-stage both RT (HR=0.13, 95% CI: 0.04-0.45, P=.001) and TN-stage 3 (HR=8.92, 95% CI: 1.47-54, P=.017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra-MLN involvement was excluded. When intra-MLN was included, multifocality became insignificant but TN-stage 3 correlated with OS (HR=8.59, 95% CI: 1.06-69.71, P=.044). Positive intra-MLN is an independent factor in predicting both RFS and OS.

Breast cancer section analysis correlates with sentinel lymph node biopsies: Precision and topographic anatomy.

The mainstream treatment of breast cancer is radical mastectomy accompanied with Axillary Lymph Node Dissection (ALND). Lately, more conservative methods accompanied by adjuvant radiotherapy have been gradually replacing radical modalities. The Sentinel Lymph Node Biopsy (SLNB) has been considered such a valuable alternative to surgery conservative approach. To assess the agreement between SLNB in breast cancer patients and pathology results following ALND and to provide correlation between the sentinel lymph nodes (SLN) anatomical topography and biopsy positivity according to SLNBs. Two hundred female breast cancer patients (31 to 83 years of age) underwent partial or simple mastectomy with or without subsequent ALND. All patients were randomized against selection criteria and underwent SLNB. In a set of 200 patients, 96.3% presented identical results between SLNB and pathology. 36% of them were confirmed with positive SLN through both approaches. Regarding the SLN topographic anatomical position, 67.3% of samples were located in the front axillary position, 24.5% in the front thoracic position, whereas 6.1% was located in the central axillary position. The correlation between the SLN topographic anatomical position and the pathology results, revealed that the majority of the SLN accumulates in the front axillary region. A larger patient population will statistically support this association.

Positive sentinel node in luminal A-like breast cancer patients - implications for adjuvant chemotherapy?

Background: In luminal A-like breast cancer, the indication for adjuvant chemotherapy still is largely based on lymph nodestatus. Sentinel node (SN) positive patients who are no longer recommended an axillary lymph node dissection (ALND) risk undertreatment, especially if they have ≥4 lymph node metastases (LNMs).Aim: To quantify the group of SN positive luminal A-like patients with ≥4 LNMs and to investigate if the ratio between positive SNs and examined SNs (SN ratio) can provide information of the axillary tumor burden.Material and methods: Nearly 370 patients between 2014-2016 in Western Sweden with a clinically node-negative invasive breast cancer treated with both SNB and subsequent ALND were included. SNB findings were compared to ALND findings and the ability of the SN ratio to describe the axillary tumor burden was evaluated using multivariable analysis.Results: In total,17.6% of patients with luminal A-like tumors had ≥4 LNMs. The SN ratio was statistically significant for predicting ≥4 LNMs among luminal A-like patients (p = .013, OR 1.89 (95% CI 1.14–3.12) per 0.1 increment in SN ratio).Conclusions: One sixth of patients with SN positive luminal A-like tumors risk undertreatment. The SN ratio may aid in identifying many of these patients.

Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in Patients with One or Two Lymph Node Metastases.

PurposeSentinel lymph node biopsy (SLNB) is a standard axillary surgery in early breast cancer. If the SLNB result is positive, subsequent axillary lymph node dissection (ALND) is a routine procedure. In 2011, the American College of Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in early breast cancer with one or two positive sentinel lymph nodes. The purpose of this study was to compare outcomes among Korean patients with one or two positive axillary lymph nodes in the final pathology who did and did not undergo ALND.MethodsA total of 131,717 patients from the Korea Breast Cancer Society registry database received breast cancer surgery from January 1995 to December 2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes, and having received breast-conserving surgery (BCS), whole breast radiation therapy, and no neoadjuvant therapy. We analyzed the differences in disease-specific survival (DSS) and overall survival (OS) between patients who received SLNB only and those who underwent SLNB+ALND.ResultsA total 4,442 patients met the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in the SLNB+ALND group. There were no differences in DSS and OS between the two groups (p=0.378 and p=0.925, respectively). The number of patients who underwent SLNB alone for one or two positive lymph nodes increased continuously from 2004 to 2014.ConclusionKorean patients with early breast cancer and 1 or 2 positive axillary lymph nodes who received BCS plus SLNB showed no significant difference in DSS and OS regardless of whether they received ALND. The findings of this retrospective study demonstrate that omitting ALND can be considered when treating selected patients with early breast cancer who have one or two positive lymph nodes.

Is extracapsular nodal extension in sentinel nodes a predictor for nonsentinel metastasis and is there an impact on survival parameters?-A retrospective single center cohort study with 324 patients

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.

Impact of receptor phenotype on nodal burden in patients with breast cancer who have undergone neoadjuvant chemotherapy.

BackgroundOptimal evaluation and management of the axilla following neoadjuvant chemotherapy (NAC) in patients with node‐positive breast cancer remains controversial. The aim of this study was to examine the impact of receptor phenotype in patients with nodal metastases who undergo NAC to see whether this approach can identify those who may be suitable for conservative axillary management.MethodsBetween 2009 and 2014, all patients with breast cancer and biopsy‐proven nodal disease who received NAC were identified from prospectively developed databases. Details of patients who had axillary lymph node dissection (ALND) following NAC were recorded and rates of pathological complete response (pCR) were evaluated for receptor phenotype.ResultsSome 284 patients with primary breast cancer and nodal metastases underwent NAC and subsequent ALND, including two with bilateral disease. The most common receptor phenotype was luminal A (154 of 286 tumours, 53·8 per cent), with lesser proportions accounted for by the luminal B–Her2 type (64, 22·4 per cent), Her2‐overexpressing (38, 13·3 per cent) and basal‐like, triple‐negative (30, 10·5 per cent) subtypes. Overall pCR rates in the breast and axilla were 19·9 per cent (54 of 271 tumours) and 37·4 per cent (105 of 281) respectively. Axillary pCR rates were highest in the Her2‐overexpressing group (27 of 35, 77 per cent) and lowest in the luminal A group (35 of 153, 22·9 per cent) (P < 0·001). Nodal burden (median number of positive nodes excised) was lower in the Her2‐overexpressing group compared with the luminal A group (0 versus 3; P < 0·001).ConclusionHer2 positivity was associated with increased rates of axillary pCR and reduced nodal burden following NAC.

Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases

PurposeThe aim of this study was to compare disease-free survival (DFS) and overall survival (OS) between clinically node-positive breast cancer patients, treated with neoadjuvant chemotherapy (NAC), with axillary pathologic complete response (ypN0), residual axillary isolated tumor cells or micrometastases (ypNitc/mi), and residual axillary macrometastases (ypN1-3).MethodsAll patients diagnosed with clinically node-positive primary invasive breast cancer treated with NAC and subsequent axillary lymph node dissection between 2005 and 2008 were retrospectively analyzed. Data were obtained from the Netherlands Cancer Registry. Patients were stratified by final pathological axillary status: ypN0, ypNitc/mi, or ypN1-3. The main outcome measures DFS and OS were analyzed using Kaplan–Meier survival analysis. Uni- and multivariable cox regression analyses were used to determine independent predictors for DFS and OS.ResultsA total of 1347 patients were included. Pathologic nodal status was ypN0 in 22.2%, ypNitc/mi in 3.8%, and ypN1-3 in 74.0% of patients. Overall, 5-year DFS was 57.8% and mean OS was 7.4 years. DFS and OS were comparable between ypN0 and ypNitc/mi (HR 1.38 (0.40–4.79, p = 0.613) and HR 0.92 (0.27–3.09, p = 0.889), respectively), but significantly different between ypN0 and ypN1-3 (HR 1.78 (1.06–3.00, p = 0.031) and HR 1.70 (1.07–2.71, p = 0.026), respectively).ConclusionsClinically node-positive patients, treated with NAC, with axillary nodal status ypN0 or ypNitc/mi carry similar prognosis regarding DFS and OS. Axillary nodal status ypN1-3 is associated with a less favorable prognosis. Future studies should consider ypN0 and ypNitc/mi as one entity.

Axillary Management of Stage II/III Breast Cancer in Patients Treated with Neoadjuvant Systemic Therapy: Results of CALGB 40601 (HER2-Positive) and CALGB 40603 (Triple-Negative)

Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from 2 NST trials: HER2-positive (Cancer and Leukemia Group B [CALGB] 40601) and triple-negative (CALGB 40603). Axillary evaluation pre- and post-NST was per the treating surgeon and could include sentinel node biopsy. Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND). We report pre-NST histopathologic nodal evaluation and post-NST axillary surgical procedures with correlation to clinical and pathologic nodal status. Seven hundred and forty-two patients were treated, 704 had complete nodal data pre-NST and post-NST. Pre-NST, 422 (60%) of 704 patients underwent at least 1 procedure for axillary node evaluation (total of 468 procedures): fine needle aspiration (n= 234; 74% positive), core needle biopsy (n= 138; 72% positive), and sentinel node biopsy (n= 96; 33% positive). Pre-NST, 304 patients were considered node-positive. Post-NST, 304 of 704 patients (43%) underwent sentinel node biopsy; 44 were positive and 259 were negative (29and 36 patients, respectively, had subsequent ALND). Three hundred and ninety-one (56%) patients went directly to post-NST ALND and 9 (1%) pre-NST node-positive patients had no post-NST axillary procedure. Post-NST, 170 (24%) of the 704 patients had residual axillary disease. Agreement between post-NST clinical and radiologic staging andpost-NST histologic staging was strongest for node-negative (81%) and weaker for node-positive (N131%, N2 29%), with more than half of the clinically node-positive patients found to be pathologic negative (p < 0.001). Our results suggest there is no widely accepted standard for axillary nodal evaluation pre-NST. Post-NST staging was highly concordant in patients with N0 disease, but poorly so in node-positive disease. Accurate methods are needed to identify post-NST patients without residual axillary disease to potentially spare ALND.

Accuracy of axillary ultrasound after different neoadjuvant chemotherapy cycles in breast cancer patients.

BackgroundThis study determined whether axillary ultrasound (AUS) accurately predicted the status of axillary lymph nodes of patients who received different number of cycles of neoadjuvant chemotherapy (NAC).Materials and MethodsFrom 2008 to 2015, 656 cases of patients with breast cancers who received NAC and had subsequent axillary lymph node dissection were included in this study. The findings of preoperative AUS were tested by pathological examination. We evaluated the sensitivity, specificity and accuracy of AUS for patients who received two-, four-, and six-cycle NAC.ResultsIn the two-cycle subgroup, the sensitivity (Sn), specificity (Sp) and diagnostic odds ratio (DOR) were 80.2% (95% CI: 74.3%-86.2%), 61.4% (95% CI: 48.8%-74.0%) and 6.64 (95% CI: 3.36-12.4) respectively. In the four-cycle subgroup, the Sn, Sp and DOR were 69.7% (95% CI: 62.2%-77.1%), 66.1% (95% CI: 53.7%-78.5%) and 4.47 (95% CI: 2.32-8.62), respectively. In the six-cycle subgroup, the Sn, Sp and DOR were 56.7% (95% CI: 49.5%-64.0%), 74.5% (95% CI: 62.8%-87.2%) and 3.83 (95% CI: 1.863-7.86), respectively. Furthermore, the patients with normal AUS findings after six cycles of NAC have few positive nodes than patients with suspicious findings (p < 0.001).ConclusionPreoperative AUS is a potentially useful imaging modality to predict the pathologic status of the axillary within four cycles of NAC. Although the accuracy is lower for patients who completed six cycles of NAC than that who received four- and two- cycles, the number of positive lymph nodes for patients with normal findings on AUS is low.

Abstract P3-01-14: A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients

Abstract Background: Completion of axillary lymph node dissection (ALND) was long lasting standard in patients with non-metastatic primary breast cancer (PBC) and axillary sentinel lymph node (SLN) involvement. However, this approach is currently questioned since recent prospective trials have found that some SLN-positive women with PBC might not benefit from subsequent ALND. Nomograms that estimate the probability of further non-sentinel lymph node (NSLN) metastases could guide clinical decisions. Methods: We compared the predictability of three different nomograms (MSKCC, Stanford University, Cambridge) on the NSLN status with an own logistic regression model in a training and validation set. SLN-positive women who underwent primary surgery including ALND at Tuebingen University, Germany, between 06/2005 - 12/2009 (training set) and 01/2010 - 02/2012 (validation set) were available for this analysis. The area under the receiver operating characteristics (ROC) curve was calculated for each nomogram. Results: 295 and 175 patients were included into the training and validation set, respectively. Of these 118 (40%) and 57 (33%) patients were NSLN-positive. Variables within our model were tumor size, proportion of positive SLNs, size of SLN metastases, lymphangiosis carcinomatosa, multicentricity and extracapsular invasion. The respective area under the ROC curve values for the MSKCC / Stanford University / Cambridge / own regression model were 0.73 / 0.70 / 0.63 / 0.75 in the training set and 0.73 / 0.66 / 0.52 / 0.73 in the validation set. Conclusion: The predictability of our logistic regression model was comparable to the MSKCC nomogram and superior to the Stanford University and Cambridge nomogram. Although a training and a validation set was used, further testing on an independent patient population is warranted. Citation Format: Hartkopf AD, Brucker SY, Helms G, Henzel M, Hahn M, Wallwiener M, Schoenfisch B, Taran F-A, Fehm TN. A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-14.