Axillary Lymph Node Dissection Group Research Articles

Ten-year outcomes of targeted axillary surgery after neoadjuvant chemotherapy in breast cancer.

600 Background: When pathological complete response (pCR) is achieved in node-positive breast cancer after neoadjuvant chemotherapy (NAC), identifying traces of the previous lesion becomes challenging which makes accurate surgery difficult. We conducted targeted axillary surgery (TAS) in node-positive breast cancer after NAC, which involves accurately targeting the lymph nodes where metastasis occurred and performing surgery using a less extensive method. The 10-year outcomes were compared with those of patients who underwent conventional axillary lymph node dissection (ALND). Methods: We conducted a retrospective analysis of 235 patients with cT1-3N1-2 breast cancer who received NAC from 2012 to 2017. In this cohort, 78 patients underwent TAS only, and 157 underwent conventional ALND, including 31 patients who initially received TAS followed by additional ALND. Oncologic results, including locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were assessed over a 10-year follow-up period. Survival outcomes for all patients and each subtype were analyzed using Kaplan-Meier survival methods. Results: The TAS group had significantly more postmenopausal patients (p=0.022), and the most common type of breast cancer was invasive ductal carcinoma [TAS: 75 (96.2%); ALND: 157 (100.0%)]. There was no statistical difference in the T stage and the number of lymph nodes suspected of metastasis at diagnosis (p=0.062, 0.985). Mastectomy was performed in 60.3% of patients in the TAS group and 93.0% in the ALND group (p<0.001), and 68 (87.2%) of the TAS group and 41 (26.1%) of the ALND group received additional axillary radiotherapy (p=0.019). There was no significant difference in oncologic outcomes between the TAS and ALND groups in all patients (LRFS, p=0.673; DMFS, p=0.729; OS, p=0.396) and based on subtypes, including hormone receptor (HR)-positive, HER2-positive, and triple-negative breast cancer (TNBC). In the HR-positive breast cancer group, the TAS and ALND groups showed very similar trends (LRFS, p=0.954; DMFS, p=0.993; OS, p=0.617). In HER2-positive breast cancer, although not statistically significant, the survival outcomes were better in the TAS group than in the ALND group (LRFS, p=0.967; DMFS, p=0.999; OS, p=0.423). However, the OS in the TAS group for TNBC was lower than that in the ALND group, though not significantly (LRFS, p=0.411; DMFS, p=0.697; OS, p=0.210). Conclusions: This study demonstrates that TAS is comparable to ALND in terms of 10-year oncological outcomes across different types of node-positive breast cancer, suggesting its potential as a viable alternative. However, further research focusing on patient quality of life and postoperative complications is essential to establish TAS as a superior surgical option to ALND.

Is a completion axillary dissection in patients with early breast cancer with a positive sentinel node necessary? An NCDB-based trial emulation of ACOSOG Z0011.

e12592 Background: The ACOSOG Z0011 Study is a practice-changing phase III clinical trial that promotes the de-escalation of axillary surgery in early breast cancer patients, which supports no completion axillary lymph node dissection (ALND) in clinically node negative patients with 1 or 2 positive sentinel lymph nodes (pSLN). Strong evidence for patients with 3 positive SLN was still lacking. We emulated the Z0011 trial using the National Cancer Database (NCDB) to validate the post-trial evidence in the real-world setting followed by a deeper investigation in the subgroups by the number of pSLN. Methods: NCDB PUF 2020 was queried for clinical T1-2 N0 M0 breast cancer patients diagnosed 2010-2017. The inclusion and exclusion criteria were the same as in the Z0011 trial except for the inclusion of 3 positive sentinel lymph nodes. Sentinel lymph node biopsy (SLNB) alone and ALND were defined using Site-Specific Factor 19. The primary endpoint, overall survival (OS), was modeled by the Cox proportional hazard model. The propensity score-based average treatment effect on the treated (ATT) weighting schema was implemented to generate pseudo samples based on this eligible study population and its subgroups as pSLN = 1, 2, and 3, where covariate balance between the two cohorts was achieved for all observed demographic and disease characteristics. Results: 25,774 patients were included in the analysis. 20311 (78.8%) patients were in the SLNB alone group, and 5463 (21.2%) patients were in the ALND group respectively. The utility rate of SLNB increased steadily over the years from 53.7% in 2010 to 91.0% in 2017. The median age was 60, which was older than that in the Z0011 trial (55). The median follow-up time was 6.78 [95% CI: 4.98-8.81] years. By multivariable analysis using the original sample, SLNB alone and the ALND group had similar survival (HR = 0.99 [95% CI: 0.90-1.09]; P = 0.83). By ATT weighting, the SLNB group had significantly improved survival (HR= 0.88 [95% CI: 0.82-0.95]; P = 0.001). The magnitude of HR is close to that in the Z0011 trial (HR= 0.87 [95% CI: 0.62-1.23]), but the statistical significance was mainly driven by a much larger sample size in this study. In the subgroup ATT weighting analysis for pSLN = 1, the SLNB group had significantly better survival compared to the ALND group (HR = 0.85 [95% CI: 0.79-0.93]; P < 0.001). Survival was equivalent for subgroup patients with pSLN = 2 (HR = 1.04 [95% CI: 0.91-1.19]; P = 0.54), while in the subgroup of pSLN = 3 patients, the SLNB group had a significantly worse survival when compared to the ALND group (HR, 1.22 [95% CI, 1.04-1.45]; P = 0.02). Conclusions: This NCDB-based Trial-Emulation study validates the result of the ACOSOG Z0011 clinical trial through a post-trial and real-world setting, where we confirmed that patients with 1 or 2 pSLN are suitable for SLNB alone, but for patients with 3 pSLN, ALND may still maintain a viable option.

Utility of axillary surgery in patients with de novo metastatic breast cancer undergoing surgery of the primary site.

1086 Background: Approximately 6% of patients have de novo metastatic breast cancer (MBC) for whom surgery is reserved for special circumstances since it confers no survival benefit. The prospective studies evaluating surgery of the primary site in MBC recommended standard surgical management of the axilla. However, it is unclear whether axillary surgery is of any utility among these patients. We sought to evaluate the survival benefit of axillary surgery in MBC patients undergoing primary site surgery. Methods: From the National Cancer Database (2012-2020), we identified patients aged 18-79 with MBC undergoing surgery of the primary site and grouped patients according to axillary surgery performed: none, sentinel lymphadenectomy (SLNB), or axillary lymph node dissection (ALND) with or without SLNB. We performed a landmark analysis beginning 12 months after diagnosis to assess overall survival (OS) and used Cox regression to adjust for clinicodemographic characteristics. Results: We identified 7,808 patients, 20.2% of whom had no axillary surgery, 16.3% had SLNB, and 63.5% had ALND. Of the patients who had axillary surgery, 26.3% were pN0. Patients who had no axillary surgery, were older (mean 57.2 vs 60.3 years), more likely to have tumor histology other than ductal or lobular (8% vs. 4%), be cN0 (28% vs. 20%), less likely to have bone-only metastases (36% vs. 44%) and undergo breast-conserving surgery (49% vs. 24%) [all p<0.001]. The mean and median number of positive nodes was 1.3±2.3 in the SLNB, and 5.9±6.8 in the ALND group. 36-month adjusted survival estimates were 71.4%, 66.5%, and 58.0% for SLNB, ALND, and no axillary surgery groups, respectively. On univariate analysis and after adjusting for clinicodemographic features, both SLNB and ALND remained independently associated with improved OS when compared with no surgery (Table). Conclusions: As in prior retrospective analyses of surgery for the primary site, we found that the performance of axillary surgery in MBC patients was associated with improved OS. Selection bias is likely a contributing factor as surgeons are more likely to recommend axillary surgery for patients with a better functional status. Of concern is the number of MBC patients being exposed to the morbidity of ALND who are ultimately pN0, and thus derived no benefit. These findings highlight the need to carefully weigh the risks and benefits before performing axillary surgery. Prospective studies evaluating axillary surgery are needed to validate these results. [Table: see text]

Abstract PO4-22-08: Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study

Abstract Background Targeted axillary sampling (TAS) is a new surgical concept for the assessment of axillary lymph node status in breast cancer that is hypothesized to be more effective at minimizing postoperative morbidities than axillary lymph node dissection (ALND), provided the metastatic axillary lymph node can be accurately detected without missing data; however, the oncologic outcomes over long-term follow-up have not been sufficiently investigated. This was a retrospective analysis to evaluate the 10-year oncologic outcomes in T1-3N1 breast cancer after TAS. Methods Clinically, we defined TAS as removal of a bunch of ALNs located around SLNs and targeted LNs, but without full exposure of the axillary vein, long thoracic nerve and thoracodorsal nerve. Between 2008 and 2013, 230 female patients with cT1-3N1 breast cancer underwent breast and axillary surgery (ALND, n = 171; TAS, n = 59) at our institute. After TAS was applied, additional axillary radiotherapy was performed. Various postoperative complications, including postoperative seroma, lymphedema, and 10-year oncological outcomes, were evaluated and compared between the ALND and TAS groups. Results Although overall survival during the 10-year follow-up period was better in the TAS group, there was no statistically significant difference in oncologic outcomes, including locoregional recurrence, distant metastasis, and overall survival (p = 0.395, 0.818, and 0.555, respectively). Furthermore, the incidence of lymphedema on the ipsilateral arm was significantly higher in the ALND group (p < 0.001). Conclusions The 10-year oncological outcomes of TAS were not inferior to those of conventional ALND in T1-3N1 breast cancers; however, the incidence of lymphedema was significantly higher in the ALND group. Citation Format: Byeongju Kang, Jeeyeon Lee, Yee Soo Chae, Ho Yong PARK, Jin Hyang Jung. Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective 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 PO4-22-08.

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Changes in lymph node surgery in breast cancer and preoperative drug prescription analysis for postoperative pain management: A retrospective, cross-sectional study.

This study aimed to investigate the changes in lymph node surgery types and prescription patterns of postoperative medications for pain management in patients with breast cancer using national health insurance claim data from South Korea. The study population comprised patients with at least one record of a principal diagnosis of breast cancer (ICD-10 code: C50) from the national health insurance claim database between 2010 and 2019. Patients who underwent mastectomy or lumpectomy only once were selected for the analysis. Patients who underwent axillary lymph node dissection (ALND) with mastectomy or lumpectomy on the day of surgery were included in the ALND group, whereas those who underwent sentinel lymph node biopsy (SLNB) were included in the SLNB group. Prescription records of opioids before, after and on the date of breast cancer surgery were collected and categorized according to the opioid type. Multivariate logistic regression modeling was used to compare postoperative opioid prescriptions. The proportion of those undergoing ALND among 3,080 patients decreased consistently after 2014, while the proportion undergoing SLNB increased. Although the rate of pain medication prescription on the day of surgery was similar between the two groups, the rate of prescription of postoperative pain medication and anticancer agents was lower in the SLNB group than in the ALND group. Logistic regression modeling showed that the SLNB group had lower odds of receiving opioids than did the ALND group (Odds ratio (OR) = 0.727, Confidence Interval (CI) = 0.546-0.970). A consistent trend was observed when the model was adjusted for neoadjuvant chemotherapy and the use of preoperative pain medications (OR = 0.718, CI = 0.538-0.959). To manage postoperative pain and prevent chronic pain with minimal side effects, sufficient discussion among clinicians, patients, and other healthcare professionals is imperative, along with adequate treatment planning.

Shoulder dysfunction after partial mastectomy and mini-latissimus dorsi or thoracodorsal artery perforator flaps for breast cancer according to the type of axillary surgeries

Background Breast cancer is the most common cancer type among women and can lead to death. Over the past few decades, there has been a significant change in the surgical management of breast cancer. The aim of this study is to assess how shoulder function was affected by reconstruction using latissimus dorsi mini flap (LDMF) and thoracodorsal artery perforator (TDAP) flaps following partial mastectomy according to surgeries to axilla. Patients and methods This was a prospective randomized study carried out on 40 consecutive female patients, complaining of early stages of breast cancer (stages I, II), undergo partial breast resection and with small tumor to breast volume ratio. All patients were randomized into two equal groups. Group I: early breast cancer (stages I, II) who underwent mastectomy defect by either TDAP flap. Group II: early breast cancer (stages I, II) who underwent mastectomy LDMF. Axillary surgeries were done to each group either sentinel lymph node biopsy dissection (SLND) or axillary lymph node dissection (ALND). Results Shoulder mobility affection 6 months postoperative was significantly higher in LDMF group than TDAP flap group (P=0.045). Regarding relation between types of lymph node surgeries and shoulder mobility affection 3–6 months postoperative, shoulder mobility affection was significantly different among the four groups as affected although ALND and LDMF group was higher. Relation between types of lymph node surgeries and effect on shoulder mobility 6 months, shoulder mobility was normal in 16 (72.73%) patients in sentinel lymph node biopsy (SLNB) and in seven (38.89%) patients in ALND and effected in six (27.27%) patients in SLNB and in 11 (61.11%) patients in ALND. Regarding shoulder mobility, affection was significantly higher in ALND than SLNB (P=0.031). Conclusions The LDMF approach with ALND is with higher shoulder mobility affection in postoperative follow-up after partial mastectomy than LDMF with SLND, TDAP flap with ALND, and TDAP flap with SLND. According to the different types of axillary surgery, ALND had higher shoulder mobility affection.

Oncological Safety of Skipping Axillary Lymph Node Dissection in Patients with Clinical N0, Sentinel Node-Positive Breast Cancer Undergoing Total Mastectomy

ObjectiveThis study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive.MethodsThis study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group.ResultsMean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70–2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69–5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02).ConclusionCollectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.

The Impact of Sentinel Lymph Node Biopsy on Female Patients With T3-4c Breast Cancer and 1-2 Positive Lymph Nodes: A Population-Based Cohort Study

PurposeThis study aimed to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in patients diagnosed with cT3-4c breast cancer with no more than 2 positive sentinel lymph nodes. MethodsUsing data from the Surveillance, Epidemiology, and End Results (SEER) database, this retrospective study identified patients diagnosed with T3-4c breast cancer between 2010 and 2015. These patients were then categorized into 2 groups: the SLNB group, which underwent examination of 1-5 regional lymph nodes and the axillary lymph node dissection (ALND) group, which underwent examination of ≥10 regional lymph nodes. Propensity score matching analysis was used to assess the efficacy of SLNB in cT3-4c patients. ResultsA total of 1139 patients were included in the analysis, with 423 and 716 patients in the SLNB and ALND groups, respectively. The 10-year overall survival (OS) and breast cancer-specific survival (BCSS) rates in the SLNB group were 66.1% and 76.3%, respectively, compared with 66.0% and 73.8%, respectively. Statistical analysis revealed no significant differences between the 2 groups in terms of OS (HR = 1.00, 95% CI = 0.80-1.25, P = .997) and BCSS (HR = 1.08, 95% CI = 0.83-1.41, P = .551). Even after 1:1 propensity score matching, there were no significant differences in OS (HR = 0.87, 95% CI = 0.65-1.16, P = .341) and BCSS (HR = 0.82, 95% CI = 0.59-1.16, P = .266) between the 2 groups. ConclusionThis study demonstrates that SLNB does not adversely affect the survival of cT3-4c breast cancer patients with 1-2 sentinel lymph node metastases.

Patterns of completion axillary dissection for patients with cT1-2N0 breast cancer undergoing total mastectomy with positive sentinel lymph nodes.

The ACOSOGZ0011 trial found that overall survival (OS) for patients with 1-2 positive nodes undergoing sentinel lymph node biopsy-alone (SLNB) was noninferior to completion axillary lymph node dissection (ALND), but excluded patients undergoing mastectomy. Our study examined patterns of ALND and its relationship with OS for SLNB-positive patients undergoing mastectomy. The National Cancer Database was queried (2010-2017) for patients with cT1-2N0 breast cancer undergoing mastectomy with positive sentinel lymph nodes. Clinical data were compared. Of 20 001 patients, 11 574 (57.9%) underwent SLNB + ALND, and 8427 (42.1%) had SLNB-alone. The SLNB + ALND group had more positive nodes (mean 2.6 vs. 1.3, p < 0.001) and more frequently received nodal radiation (33.4% vs. 28.9%, p < 0.001). Patients diagnosed in later years were less likely to undergo ALND (2010: reference; 2017:odds ratio: 0.29, 95% confidence interval [CI]:0.25-0.33, p < 0.001). ALND (hazard ratio [HR]: 0.97, 95%CI: 0.89-1.06, p = 0.49) and nodal radiation (HR: 0.92, 95%CI: 0.83-1.02, p = 1.06) were not independently associated with OS. Propensity-score matched 5-year OS was similar (SLNB + ALND: 90.9% vs.SLNB-alone: 90.3%, p = 0.65). For patients undergoing mastectomy for cT1-2N0 breast cancer with positive SLNB, SLNB-alone was common and increased over time. Axillary radiation was not routinely delivered in the SLNB-alone group. Completion ALND and nodal radiation were not associated with improved survival.

Is it the Type of Axillary Surgery or the Number of Removed Lymph Nodes That Increases the Risk of Breast Cancer Related Lymphedema (BCRL)? Results from a Prospective Screening Trial

Axillary surgery has been identified as the main risk factor for BCRL regardless the delivery of regional nodal radiation (RLNR). Yet it remains unknown if it is the type of axillary surgery or the number of removed lymph nodes (LN) that increases BCRL risks. Between 2008 and 2021, 3,350 patients (pts) who received surgery for breast cancer were enrolled in a lymphedema screening trial. Patients with bilateral breast cancer or without axillary surgery were excluded. Perometry was used to assess limb volume preoperatively in all patients. BCRL was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. The cohort was divided by axillary surgery type: axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). Radiation was delivered using 3D conformal technique and RLNR was defined as the usage of anterior supraclavicular field. No hypofractionation was used and doses ranged between 50 and 50.4 Gy in 25-28 fractions. Multivariable Cox proportional hazard models compared the cumulative incidence of BCRL and local failure between different patient groups. After applying inclusion criteria, 2,623 pts were available with overall median follow-up s of 6.1 years. Of the entire cohort, 709 (27%) had ALND with a median of 16 LN removed, while 1,914 (73%) received SLNB only with a median of 2 LN removed. The median number of malignant LN and patients receiving RLNR was higher in ALND group compared to SLNB only group. Frequency distribution analysis showed that the main overlap between ALND and SLNB only groups happen in the range of 3-11 LN removed. Therefore, the primary analysis focused only on pts with 3-11 LN across both groups (n = 690: ALND n = 140, SLNB n = 550). The multivariable model adjusted for BMI, RLNR, age and breast surgery showed that in this group with 3-11 LN removed in both cohorts, ALND remained significantly associated with BCRL (HR: 4.2, p<0.0001). Separate analyses for the entire SLNB only group and ALND groups were conducted to evaluate if the BCRL risk increases per each removed LN within the same axillary surgery group. The multivariable analysis for SLNB only pts(N = 1,914) showed that for each LN removed the risk of BCRL did not increase significantly (HR:1.06, p = 0.3), similarly for ALND group (N = 709) for each LN removed (HR:1.02, p = 0.08). For pts with pathologic N2-N3 disease and clinical node negative without neoadjuvant chemotherapy receiving ALND, the number of LN removed did not significantly improve neither Local control (HR:1.02, p = 0.8) nor distant disease survival (HR:1.01, p = 0.6). ALND procedure per se is the main risk factor for BCRL not the number of LNs removed. For high-risk pts with >N2 disease, aggressive ALND did not improve tumor outcome. De-escalation with targeted axillary sampling followed by RLNR should be evaluated. Future lymphedema research should account for type of axillary surgery instead of number of LNs removed as a factor. (NCT01521741).

The Efficacy of Axillary Reverse Mapping for the Prevention of Lymphedema.

Lymphedema (LE) is the most notable complication of axillary surgery. The axillary reverse mapping (ARM) technique was created to decrease LE. This study aims to evaluate a single surgeon's experience with ARM in patients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for breast cancer. We retrospectively analyzed patients who underwent SLNB or ALND. Tumor characteristics and treatments received were evaluated. Surgical intervention and use of ARM were compared to assess LE rates. A subgroup analysis was also performed of patients who underwent NAC. LE was initially reported in 7.1% (n = 10) of patients; 3.3% (n = 4) with SLNB and 35% (n = 6) with ALND. At initial follow-up, LE was reported 16.4% more often in patients who underwent ALND with no ARM, and 38.8% more often in patients who underwent ALND plus ARM. An increased risk of LE was found in patients treated with ALND (OR = 16.0, P < .001). All patients who underwent ARM were 12.75% more likely to develop LE if they received NAC (P < .05). Patients in the ALND group who also received NAC were more likely to undergo ARM as compared with patients in the SLNB group (P < .01). Our study showed that ARM failed to decrease the incidence of LE. Until better surgical outcomes are shown for the prevention of LE using ARM, other approaches should be utilized. However, larger prospective studies are needed to evaluate ARM.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer

The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Safety of Targeted Axillary Dissection After Neoadjuvant Therapy in Patients With Node-Positive Breast Cancer

The increasing use of neoadjuvant systemic therapy (NST) has led to substantial pathological complete response rates in patients with initially node-positive, early breast cancer, thereby questioning the need for axillary lymph node dissection (ALND). Targeted axillary dissection (TAD) is feasible for axillary staging; however, data on oncological safety are scarce. To assess 3-year clinical outcomes in patients with node-positive breast cancer who underwent TAD alone or TAD with ALND. The SenTa study is a prospective registry study and was conducted between January 2017 and October 2018. The registry includes 50 study centers in Germany. Patients with clinically node-positive breast cancer underwent clipping of the most suspicious lymph node (LN) before NST. After NST, the marked LNs and sentinel LNs were excised (TAD) followed by ALND according to the clinician's choice. Patients who did not undergo TAD were excluded. Data analysis was performed in April 2022 after 43 months of follow-up. TAD alone vs TAD with ALND. Three-year clinical outcomes were evaluated. Of 199 female patients, the median (IQR) age was 52 (45-60) years. A total of 182 patients (91.5%) had 1 to 3 suspicious LNs; 119 received TAD alone and 80 received TAD with ALND. Unadjusted invasive disease-free survival was 82.4% (95% CI, 71.5-89.4) in the TAD with ALND group and 91.2% (95% CI, 84.2-95.1) in the TAD alone group (P = .04); axillary recurrence rates were 1.4% (95% CI, 0-54.8) and 1.8% (95% CI, 0-36.4), respectively (P = .56). Adjusted multivariate Cox regression indicated that TAD alone was not associated with an increased risk of recurrence (hazard ratio [HR], 0.83; 95% CI, 0.34-2.05; P = .69) or death (HR, 1.07; 95% CI, 0.31-3.70; P = .91). Similar results were obtained for 152 patients with clinically node-negative breast cancer after NST (invasive disease-free survival: HR, 1.26; 95% CI, 0.27-5.87; P = .77; overall survival: HR, 0.81; 95% CI, 0.15-3.83; P = .74). These results suggest that TAD alone in patients with mostly good clinical response to NST and at least 3 TAD LNs may confer survival outcomes and recurrence rates similar to TAD with ALND.

Axillary surgery efficacy for patients with breast cancer receiving neoadjuvant chemotherapy on NSABP B40 and B41.

524 Background: Alliance A011202 is evaluating the efficacy of axillary lymph node dissection (ALND) compared to regional nodal irradiation (RNI) for patients with cN1 breast cancer who receive neoadjuvant chemotherapy (NCTX) that becomes ycN0 but remains pN+. In the absence of its publication, level I guidance does not exist regarding the optimal axillary surgery for patients receiving NCTX. We sought to evaluate outcomes across two national contemporary clinical NCTX trials based on axillary and breast response to NCTX, particularly if more aggressive surgery was associated with more favorable outcomes. Methods: With IRB approval (IRB201802781), we obtained data from NCTX trials NSABP B40 and B41. B40 enrolled women with HER2- disease, and B41 enrolled those with HER2+ disease. RNI and axillary surgery were selected at physician discretion and not protocolled. Patients received sentinel lymph node biopsy (SLNB), SLNB+ALND (S+ALND), or ALND. We examined outcomes of locoregional recurrence (LRR), distant recurrence (DR), disease free survival (DFS), and overall survival (OS). Univariable and multivariable analyses of B40 and B41 data were performed to evaluate the associations of axillary surgery with the outcomes above, adjusting for age, tumor subtype, mastectomy or not, breast pathologic complete response (pCR), axillary pCR, tumor subtype, regional nodal irradiation, and grade. Kaplan-Meier estimation was used for OS and DFS, with cumulative incidence function for LRR and DR. Results: Median follow-up for studies B40 and B41 were 4.5 and 5.1 years, respectively, including 1154 and 504 patients for analysis. A total of 786 (47%) patients were cN+, and of those, 377 had a pcR (48%). 440 (27%), 505 (31%), and 663 (41%) patients had SLNB, S+ALND, and ALND respectively. 855 (52%) and 803 (48%) patients had mastectomy and lumpectomy, respectively. 783 (51%) received RNI. For the 518 ypN+ patients on B40, 7/25 (SLNB), 69/234 (S+ALND), and 107/259 (ALND) experienced an event. DFS at 5 years was 71%, 68%, and 56% for the SLNB, S+ALND, and ALND groups respectively with ypN+ on B40. For the 112 ypN+ patients on B41, 3/6, 15/43, and 27/63 experienced an event. DFS at 5 years was 50%, 64%, and 55% for the SLNB, S+ALND, and ALND groups, respectively, with ypN+ on B41. In multivariable analyses for the combined population of B40 and B41 for LRR, DR, DFS, and OS, SLNB was never associated with a higher chance of relapse or inferior survival (HR &gt; 1) compared to S+ALND or ALND. Conclusions: Among women prospectively treated on national trials with NCTX and axillary surgery and RNI selected at physician discretion, receipt of SLNB alone was not associated with a higher likelihood of recurrence compared to S+ALND or ALND. Anticipated results of A011202 will provide level I guidance on axillary surgery for patients with cN1 disease converting to cN0 post-NCTX.

Can axillary lymph node dissection (ALND) be omitted in patients with breast cancer with persistent axillary disease after neoadjuvant chemotherapy?

e12624 Background: Axillary lymph node dissection (ALND) is the standard of care for patients (pts) with persistent node-positive (N+) disease after neoadjuvant chemotherapy (NAC). In those with a clinical response to NAC, it is appropriate to perform limited axillary surgery to evaluate axillary status, with ALND reserved for those who remain N+. We define the directed-sentinel node biopsy (dSLNB) as pre-operative localization of the previously positive lymph node combined with dual-tracer sentinel node biopsy. We hypothesize that omission of ALND in those that have residual N+ disease after NAC, is associated with less morbidity, without impacting outcomes. Methods: This is a single-institution, retrospective analysis of consecutive pts with N+ breast cancer (BC) who received NAC and dSLNB +/- ALND from 2014-2021. A clip was placed in the positive node at the time of biopsy and excised using radioactive seed localization (RSL) with an I-125 seed. Only those with persistent disease in the RSL on pathology were included (RSL+). We assessed the impact of extent of axillary surgery on primary outcomes, including recurrence, disease-free survival (DFS) and overall survival (OS), and secondary outcomes, including location of recurrence and lymphedema. Results: 156 female pts with N+ BC received NAC, underwent dSLNB +/- ALND with RSL+. Mean age was 52.1 years (SD 12.2). Median follow-up was 32.5 months (IQR 22.9-51.6). Phenotype distribution was 55.8% luminal, 21.2% HER2 positive, and 23.1% triple negative, with no difference between ALND or dSLNB. Pts who had ALND had a higher nodal stage at presentation compared to dSLNB (N1: 72.9% vs. 91.8%, N2: 20.6% vs. 8.2%, N3: 6.5% vs. 0%, p = 0.016). 90.4% received adjuvant radiation with no difference between ALND and dSLNB. Lymphedema rates were higher in the ALND group (47.7% vs. 16.3%, p &lt; 0.001). Fifteen patients died with no difference between ALND and dSLNB in overall mortality rates (9.3% vs. 10.2%, p = 1.000). Nineteen pts recurred with 73.7% occurring at distant sites (ALND 76.5% vs. dSLNB 50%, p = 0.468). There was a higher recurrence rate after ALND (15.9% vs. 4.1%, p = 0.038) as well as higher rates of extracapsular LN extension (46.7% vs. 14.9%, p &lt; .001) and breast lymphovascular invasion (49% vs. 30.4%, p = 0.035). Comparing ALND to dSLNB, there was no difference in DFS (30 months vs. 37 months, p = 0.650) or OS (36.4 months vs. 36.2 months, p = 0.982). Conclusions: For pts with persistent N+ disease in the RSL node after NAC, there was no difference in DFS or OS regardless of extent of axillary surgery. ALND led to higher rates of morbidity, namely lymphedema, but did not contribute to better outcomes. Most recurrences were distant, suggesting aggressive tumor biology as the driver for poor oncologic outcomes rather than the extent of axillary surgery. In this light, the results of the Alliance 11202 are awaited as it answers the question on a randomized, multi-institutional level.

Oncologic outcomes for different axillary staging techniques in nodal positive breast cancer undergoing neoadjuvant systematic treatment: A cancer registry study.

e12571 Background: The optimal axillary staging technique for patients with nodal positive breast cancer undergoing neoadjuvant systemic treatment (NAST) is unclear. Less invasive, targeted approaches like targeted axillary dissection (TAD) or sentinel-lymph node biopsy (SLNB) recently showed false-negative rates &lt; 10% compared to axillary lymph node dissection (ALND). Oncologic outcomes, however, are unknown. Methods: We identified nodal positive breast cancer patients undergoing NAST from 2016 to 2021 with at least 1-year follow-up and available information regarding axillary staging from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate cox regression models (adjusted for age, pN stage, pT stage, and tumor biologic subtype). Results: A total of 2403 patients with a median follow-up of 23.2-months after surgery were identified: 1963 underwent ALND, 407 underwent SLNB (in 230 cases, three or more sentinel nodes (SLNs) were removed and in 177 cases, 1-2 SLNs were removed), and 33 underwent TAD. The proportion of patients with pN+ stage within these four groups was 54%, 31%, 26%, and 35%, respectively ( P &lt; 0.001). Significant differences in iDFS between the ALND, SLNB, and TAD groups were observed (log rank P = 0.046): iDFS 2 years after surgery was 74.5% (ALND), 80.2% (SLNB ≥3 removed SLNs), 85.6% (SLNB &lt; 3 removed SLNs), and 88.4% (TAD), respectively. iDFS after 4 years was 61.5% (ALND), 69.1% (SLNB ≥3 removed SLNs), and 74.6% (SLNB &lt; 3 removed SLNs), respectively. Multivariate cox regression analysis showed no significant influence of different axillary staging techniques on iDFS: HR 0.91 (95% CI 0.55 to 1.52) for SLNB with ≥3 removed SLNs, HR 0.99 (95% CI 0.59 to 1.67) for SLNB with &lt; 3 removed SLNs (reference = ALND). Conclusions: This data suggests that ALND provides no benefit in terms of iDFS compared to targeted approaches like TAD or SLNB for patients with nodal positive breast cancer undergoing NAST. Future studies with longer-term follow-up are welcomed to fully inform this discussion.

Survival After Sentinel Lymph Node Biopsy Compared with Axillary Lymph Node Dissection for Female Patients with T3-4c Breast Cancer.

For patients with cN0 and T1-2 breast cancer, sentinel lymph node biopsy (SLNB) can provide survival results equivalent to axillary lymph node dissection (ALND). However, whether it can be performed on T3-4c patients is still controversial. Female patients diagnosed with cN0, T3-4c, and M0 breast cancer from 2004 to 2019 were identified using the surveillance, epidemiology and end results (SEER) database and divided into 2 groups, the SLNB group (1-5 regional lymph nodes examined) and the ALND group (≥10 regional lymph nodes examined). Finally, only those with pN0 disease were included in the SLNB group. The baseline differences in clinicopathological characteristics between groups were eliminated by propensity score matching (PSM). We also conducted subgroup analyses according to age, overall TNM stage, breast cancer subtypes, surgical approaches, radiation therapy, and chemotherapy. The primary endpoint was survival. With a mean follow-up of 75 months, a total of 186 deaths were reported among 864 patients. The overall survival (OS) and breast cancer-specific survival (BCSS) in the SLNB group were 78.2% and 87.5%, respectively, and that in the ALND group were 78.7% and 87.3%, respectively. The unadjusted hazard ratio (HR) for OS and BCSS in the SLNB group (vs. the ALND group) was 0.922 (95% CI, 0.691-1.230, P = .580) and 0.874 (95% CI, 0.600-1.273, P = .481), respectively. Besides, the OS and BCSS between the 2 groups were also similar in all subgroup analyses. SLNB may be performed on female patients with cN0, T3-4c, and M0 breast cancer.

Abstract PD15-02: PD15-02 Long Term Outcome in Patients with Nodal-Positive Breast Cancer Treated with Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy

Abstract Importance: The use of neoadjuvant chemotherapy (NAC) in the clinical care of breast cancer patients has increased considerably over recent years especially in node positive cases. For patients who have axillary nodal metastases prior to NAC, the prevailing standard of care is to undergo an axillary lymph node dissection (ALND), regardless of response to therapy. Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in patients who had clinical complete response in the axilla following NAC. This is due to the presumed high false negative rate associated with SLNB in such scenario. But there are limited data on the long term outcome of these patients who are only treated with SLNB alone. Aim: A retrospective cohort study comparing the long term outcome of breast cancer patients with clinically node positive disease (N1) but turned clinically node negative (N0) following NAC, receiving SLNB alone versus ALND. Methods: Patients who had pathologic proven N1 breast cancer (before NAC) treated with NAC and turned clinically N0 from January 2009 to December 2014 were identified from Asan Medical Center breast cancer database in South Korea. Primary endpoint was axillary recurrence rate (ARR) and secondary endpoints were disease-free survival (DFS) and overall survival (OS). These outcomes were reported for patients who had SLNB alone versus ALND. Results: 561 patients with clinically stage N1 (cN1) cancer treated with NAC and turned clinically stage N0 (cN0) were identified. 253 (45.1%) patients received SLNB only while 308 (54.9%) patients had ALND. The clinicopathological features of these patients were illustrated in Table 1. Majority of these patients received adjuvant radiotherapy, 81.2% in the SLNB group and 76.5% in the ALND group. In the pathologically stage N0 (ypN0) group, at a median follow up of 69 months, ARR was 3.0% in the SLNB only group and 1.7% in the ALND group (p=0.704). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p= 0.561 and 0.810 respectively). Median number of SLN harvested in the SLNB only group is 5 (range 1 -17). In the pathologically stage N1 (ypN1) group with only 1-2 lymph node positive for metastasis, at a median follow up of 66 months, ARR was 5.8% in the SLNB group and 4.7% in the ALND group (p=0.768). There was no significant difference in DFS and OS between the SLNB and ALND group (p=0.537 and 0.645). In the SLNB only group, the median number of positive lymph node was 1 (range 1-2), the median number of sentinel lymph node was 6 (range 2-18). Conclusion: In cN1 breast cancer patients who were converted to cN0 following NAC, axillary recurrences were rare. No statistically significant differences were noted in DFS and OS between patients with SLNB or ALND. Our findings suggest that these patients may be safely treated with SLNB only, even when there are up to 2 positive SLNs. Table 1 Clinicopathological features of breast cancer patients with nodal disease and NAC Citation Format: Sue Zann Lim, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Hee Jeong Kim. PD15-02 Long Term Outcome in Patients with Nodal-Positive Breast Cancer Treated with Sentinel Lymph Node Biopsy Alone After 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 PD15-02.

Abstract OT1-06-01: Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE

Abstract Introduction: Axillary lymph node dissection (ALND) has always been part of breast cancer (BC) treatment. However, during the past 25 years, the surgical management of the axilla has shifted towards a more conservative approach. Until now, ALND has remained the standard surgical technique when the sentinel lymph node (SLN) is macrometastatic. However, ALND may now be considered overtreatment for early-stage BC. The SINODAR-ONE trial is a prospective non-inferiority multicenter randomized study aimed at assessing the role of ALND in patients undergoing either breast-conserving surgery (BCS) or mastectomy for T1-2 BC presenting 1-2 macrometastatic SLNs. Objectives: The primary endpoint was to evaluate whether sentinel lymph node biopsy (SLNB) only was associated with clinically relevant worsening of the prognosis compared with ALND in terms of overall survival (OS). The secondary endpoint was to evaluate whether there was increased regional (lymph node recurrence) or distant recurrence in terms of recurrence-free survival (RFS) in patients with macrometastatic SLN who did not undergo ALND. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. The majority of the patients (75.2%) underwent BCS; 328 of 439 patients (74.7%) in the standard treatment arm, and 333 of 440 patients (75.7%) in the experimental treatment arm. 218 patients (24.8%) underwent mastectomy. SLN status at randomization was comparable between the two groups of treatment, with a median number of two SLNs removed and a median number of one positive SLN in both arms. The median number of non-SLNs identified at definitive histopathological evaluation was 16 (interquartile range [IQR] 12–21) in the ALND group. Overall, 193 of 439 patients (44.0%) in the standard treatment arm had additional macrometastases in the removed axillary lymph nodes. However, the median number of positive non SLNs was 0 (IQR 0–1) in the ALND group. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with a 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with a 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB only arm, respectively (p = 0.936). Conclusion: The 3-year survival and relapse rates of T1-2 BC patients with 1-2 macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND in patients undergoing BCS. However, given the low number of patients treated with mastectomy, there is no certainty that ALND omission can be extended also to this sub-group. In order to collect further evidence regarding the safety of the experimental treatment in patients candidates for mastectomy, the reopening of the enrollment of these patients as part of a single-arm experimental study started in June 2022. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Testori, Valentina Errico, Alberto Bottini, Simone Di Maria Grimaldi, Giulia Caraceni, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Davide Franceschini, Ruggero Spoto, Rosalba Torrisi, Marta Scorsetti, Armando Santoro, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE [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 OT1-06-01.