Reducing locoregional treatments in low risk early invasive breast cancer.

Does neoadjuvant systemic therapy in clinical T1-2 N0 human epidermal growth factor receptor 2-positive breast cancer increase the extent of axillary surgery?

Sentinel lymph node biopsy (SLNB) is the standard surgical approach for axillary node staging in patients with early-stage breast cancer (EBC). However, there is an increasing trend in investigating the omission of SLNB, as molecular tumor biology has become a primary determinant of systemic therapy, overshadowing the importance of nodal status. The SOAPET trial constitutes a prospective phase II study structured into two phases. In the first stage, we demonstrated that LymphPET could be utilized to screen patients to potentially forego SLNB, achieving a negative predictive value of 91%. In the second stage, SLNB was omitted for patients with a negative preoperative axillary evaluation (PAE) integrated with LymphPET. Primary endpoints were the 3-year distant disease-free survival (DDFS) and locoregional recurrence-free survival (LRRFS). A total of 304 patients were enrolled with a median age of 52.5 years (IQR 44-62 years). Of these patients, 240 (78.9%) presented with clinical T1 tumors. Among all the cases, 218 (71.7%) were classified as luminal-like breast cancer. The median follow-up was 43.5 months. The 3-year DDFS and LRRFS rates were 100% and 99.7% (95% CI 99.0-100.0), respectively. In the entire cohort, two cases (0.7%) of ipsilateral axillary node relapse, one (0.3%) ipsilateral in-breast recurrence, and one (0.3%) distant metastasis were reported. The second phase of the study corroborates the oncologic safety of omitting SLNB on the basis of PAE incorporating LymphPET. For patients with clinically node-negative EBC with high-risk characteristics, SLNB might be safely spared with the added diagnostic benefit provided by LymphPET. ClinicalTrials.Gov ID NCT04072653.

Introduction: Implant-based breast reconstruction is associated with an increased risk of ischemic complications, which may result in implant loss, suboptimal aesthetic outcomes, and delays in adjuvant oncological treatment. Additionally, axillary surgery carries a risk of upper-limb lymphedema. Indocyanine green (ICG) angiography enables more accurate real-time assessment of tissue perfusion than clinical evaluation alone, while axillary reverse mapping (ARM) facilitates the preservation of upper-limb lymphatics. The integration of these techniques reduces complications and improves both functional and aesthetic outcomes. Materials and methods: A total of 208 breast cancer patients who underwent mastectomy followed by immediate implant-based breast reconstruction were enrolled in this case-control study. The prospective intervention group received intraoperative ICG angiography at three time points and underwent ARM with ICG. Conventional surgical techniques were applied in the retrospective control group. Results: ICG angiography showed excellent diagnostic accuracy for predicting postoperative ischemic complications (AUC = 0.93, 95% CI 0.82-0.99, p < 0.001). Compared with the control group, patients in the ICG group had significantly lower rates of mastectomy skin flap necrosis (11.5% vs. 30.8%, p = 0.001), seroma (4.8% vs. 14.4%, p = 0.032), hematoma (1.9% vs. 9.6%, p = 0.033), and lymphedema (2.9% vs. 17.3%, p < 0.001). They also experienced shorter hospitalization (6.2 ± 1.9 vs. 8.0 ± 2.8 days, p < 0.001), fewer delays in adjuvant treatment initiation (16.3% vs. 32.7%, p = 0.010), and higher aesthetic satisfaction scores (81.41 ± 10.12 vs. 76.03 ± 9.74, p <0.001). Conclusions: Intraoperative indocyanine green angiography is a valuable tool for predicting ischemic complications in alloplastic breast reconstruction and is associated with reduced morbidity, fewer delays in adjuvant treatment, and improved aesthetic outcomes. Preliminary evidence suggests that axillary reverse mapping is associated with lower rates of upper-limb lymphedema.

Abstract Background: Axillary nodal status is an important prognostic factor in early breast cancer (eBC), guiding systemic treatment and postoperative radiotherapy. As axillary surgery does not significantly affect BC mortality itself, it is considered as a staging procedure in clinically node-negative (cN0) patients (pts). The Intergroup-Sentinel-Mamma (INSEMA) trial investigated the avoidance of sentinel lymph node biopsy (SLNB) in cN0 pts (Rando1) or the omission of completion axillary lymph node dissection (cALND) in pN1a(sn) pts (Rando2). The analysis of the first randomization demonstrated non-inferiority of omitting SLNB in cN0 patients undergoing breast-conserving surgery (BCS) concerning invasive disease-free survival (iDFS), meeting the trial's primary endpoint. Here we report the analysis of the second randomization. Study Design: The INSEMA trial was conducted between 2015 and 2019 in Germany and Austria. The first randomization of this prospective trial compared no axillary surgery with SLNB in pts with invasive eBC (tumor size ≤ 5 cm; c/iN0) scheduled for BCS, including postoperative whole-breast irradiation (WBI). This randomization was carried out in a 4:1 allocation (SLNB vs. no SLNB). Pts with 1-3 macrometastases in the SLNB arm underwent a second randomization in a 1:1 ratio, to either SLNB alone or cALND. The aim was to assess whether SLNB alone is non-inferior to cALND in terms of iDFS. The analysis of Rando2 was based on the per-protocol (PP) set. Due to fewer SLNB-positive patients than expected, the iDFS analysis for the second randomization was downgraded from a co-primary to a key secondary outcome following protocol amendment #5 (December 2018). The non-inferiority margin was defined as 5-year iDFS &amp;gt; 76.5% (hazard ratio (HR) &amp;lt; 1.271) for SLNB alone, compared to an expected 5-year iDFS of 81% for the cALND arm. Results: 485 pts were recruited for Rando2 (intention-to-treat (ITT) set: N=243 with cALND vs. N=242 with SLNB alone). After excluding 99 pts (mainly due to axillary surgery performed not per randomized arm), 386 pts (cALND: N=169, SLNB alone: N=217) were included in the PP set. The median follow-up (FU) is 74.2 months. The cALND cohort is characterized by higher rates for postoperative chemotherapy (39.8% vs. 33.6%, p=0.239), conventionally fractionated WBI (87.0% vs. 75.1%, p=0.004), tumor bed boost (88.8% vs. 80.6%, p=0.035), and regional nodal irradiation (36.0% vs. 20.6%, p=0.019) compared to the SLNB alone cohort. Analysis in the PP set was unable to demonstrate non-inferiority for SLNB alone compared to cALND, with an HR of 1.6]9 (95% CI: 0.98-2.94). Estimated 5-year iDFS rates are 86.6% (81.0%-90.7%) in the SLNB alone arm and 93.8% (88.7%-96.6%) in the cALND arm (log-rank p=0.058). Estimated 5-year overall survival (OS) rates are 94.9% (90.6%-97.2%) in the SLNB alone arm and 96.2% (91.7%-98.3%) in the cALND arm (log-rank p=0.663). Among the ITT set, there was also no difference in iDFS between the arms, with an HR of 1.26 (0.80-1.99) for SLNB alone compared to cALND. Estimated 5-year iDFS rates (ITT set) are 86.0% (80.6%-90.0%) with SLNB alone and 89.3% (84.3%-92.8%) with cALND, respectively (log-rank p=0.314). Locoregional recurrences (LRR) were infrequent, with 5-year cumulative incidence rates of 1.1% vs. 0.0% (p=0.405) in the SLNB alone arm compared to cALND. The safety analysis demonstrates that patients who underwent SLNB alone benefited in terms of lymphedema rate, arm mobility, and reduced arm and shoulder pain. Conclusion: No significant differences were observed between SLNB alone vs. cALND in both subsets (PP, ITT) for iDFS, OS, and LRR. These findings after a 6-year FU are representative of cN0 pts with positive SLNB and BCS; the 10-year FU data will be presented in 2029. Citation Format: T. Reimer, A. Stachs, K. Veselinovic, T. Kühn, J. Heil, S. Polata, F. Marmé, E. K. Trapp, T. Müller, G. Hildebrandt, D. Krug, B. Ataseven, R. Reitsamer, S. Ruth, H. Strittmatter, C. Denkert, I. Bekes, N. Stahl, D. Zahm, M. Thill, M. Golatta, J. Holtschmidt, M. Knauer, V. Nekljudova, S. Loibl, B. Gerber. Axillary surgery in breast cancer patients with one to three sentinel node macrometastases and breast-conserving therapy: Secondary results of the INSEMA trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-02.

Abstract Introduction: Although previous randomized controlled trials have suggested that axillary surgery may be omitted in patients with clinically node-negative breast cancer with tumor ≤ 2cm (pT1), approximately 15% of these patients were found to have lymph node (LN) metastasis. Furthermore, while these studies demonstrated that axillary surgery, including sentinel LN biopsy, does not provide a therapeutic benefit, concern remain regarding the prognostic impact of occult LN metastasis. Therefore, the aim of our study was to identify factors associated with LN metastasis in small tumors (≤ 2cm) and to analyzed its impact on recurrence. Methods: We identified patients with pT1 primary breast cancer who underwent treatment at two hospitals between September 2003 and December 2019. To ensure accurate assessment of pathologic LN metastasis, patients who received neoadjuvant systemic therapy or did not undergo axillary surgery were excluded. Multivariate analysis was performed to identify factors associated with LN metastasis and to evaluate the impact of LN metastasis on recurrence-free survival (RFS). Results: A total of 1,745 patients were included in the study, of whom 384 (22.0%) had axillary LN metastasis. In the multivariate binary logistic regression model, LN metastasis was significantly more common in tumors larger than 1cm (odds ratio [OR], 2.94; 95% confidence intervals [CI], 0.15-4.08; P&amp;lt;0.001) and in the presence of lympho-vascular invasion (OR, 4.41; 95% CI, 3.37-5.78; P&amp;lt;0.001) while it was less frequent in tumors with histology other than ductal or lobular type (OR, 0.45; 95% CI, 0.22-0.89; P=0.022). In the multivariate Cox proportional hazard model, LN metastasis was identified as a significant risk factor related with worse RFS (hazard ratio, 1.99; 95% CI, 1.26-3.14; P=0.003). In subgroup analysis, LN metastasis was associated with poor prognosis across most subgroups, with its impact being particularly pronounced in patients with tumors&amp;gt;1cm, histologic grade I or II, and the HR+/HER2- subtype. Conclusion: Our study found the factors associated with a higher likelihood of LN metastasis in small (pT1) breast tumors and confirmed that LN metastasis is associated with wore prognosis. Because the presence of LN metastasis can increase the risk of recurrence, even in small tumors, careful consideration should be given to performing axillary surgery to avoid potential undertreatment in patients with a high risk of LN metastasis. Citation Format: J. Lee, K. Yeonjoo, P. Youri, L. Young Ah, W. Joo Hyun, L. Woo Sung, K. Hee-Joon, M. Byung-In. Factors associated with lymph node metastasis and its prognostic impact in breast cancer patients with small tumors (≤2cm) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-11-02.

Abstract Background: Breast-conserving surgery followed by radiotherapy remains the standard of care for early-stage breast cancer. However, interest in minimally invasive alternatives has grown. Cryoablation is a nonsurgical, image-guided technique that induces tumor cell death through freezing and thawing, avoiding general anesthesia and hospitalization. The CRYSTAL–SIX trial (CRYoablation for Small Tumors As Local treatment – SIX) is a phase III study evaluating whether cryoablation is non-inferior to standard breast surgery in terms of locoregional control and cost-effectiveness. Two landmark trials have shaped modern de-escalated care. The SOUND trial showed that omitting axillary surgery in tumors ≤2 cm with negative axillary ultrasound was non-inferior to sentinel lymph node biopsy. The FAST-Forward trial demonstrated that 26 Gy in five fractions over one week was non-inferior to 40 Gy in 15 fractions over three weeks for local control and normal tissue effects over five years. These findings, combined with the advantages of cryoablation, led to the SIX trial design, which integrates cryoablation, omission of axillary surgery, and ultrahypofractionated radiotherapy—completing treatment in just six days. Methods: This phase III, randomized, controlled, multicenter trial compares cryoablation to breast surgery in 750 patients with unifocal, invasive breast carcinoma (≤2.0 cm, T1N0M0), visible on ultrasound and eligible for upfront surgery. Cryoablation will be performed using Cryocare® or ProSense IceCure® under local anesthesia and ultrasound guidance. Surgery includes lumpectomy or mastectomy with sentinel lymph node biopsy. Axillary surgery is omitted in the cryoablation arm. All patients will receive adjuvant treatment according to tumor biology. When indicated, radiotherapy will be delivered as 26 Gy in five fractions over one week. The study incorporates a de-escalated strategy by omitting axillary surgery, applying ultrahypofractionated radiotherapy, and using liquid biopsy for monitoring. Approved by the Ethics Committee, recruitment began in March 2025 and ends in 2030. Registered at ClinicalTrials.gov (NCT06839001). Objectives: Primary: Demonstrate non-inferiority of cryoablation vs. surgery for local treatment over five years, and compare direct treatment costs over one year. Secondary: Assess locoregional recurrence at one year, disease-free and overall survival at five years, and CTCs at baseline, six, and twelve months as prognostic and monitoring tools. Patient satisfaction will be measured via Breast-Q (1 year), and quality of life via EQ-5D. Conclusions: The CRYSTAL–SIX trial investigates cryoablation as a definitive, nonsurgical alternative to breast surgery in early-stage breast cancer. By combining cryoablation, omission of axillary surgery, and ultrahypofractionated radiotherapy, it proposes a modern, patient-centered model. If non-inferiority is confirmed, this strategy may reduce treatment burden, lower costs, and enhance quality of life without compromising oncologic outcomes. The SIX trial reflects and may help redefine current standards in de-escalated breast cancer care. Citation Format: V. M. Sanvido, L. Chinen, M. Nicola, J. O. Gomes, L. G. Barbante, A. B. Cavalcanti, A. P. Nazário. Cryoablation versus Breast Surgery in the Local Treatment of Early-Stage Breast Cancer: Protocol for the CRYSTAL-SIX Trial (CRYoablation for Small Tumors As Local Treatment) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-30.

Abstract Background: Local anesthesia with sedation (LAS) is widely used in other surgical disciplines but remains underutilized in breast-conserving surgery (BCS), where general anesthesia (GA) is still the standard [1, 2]. Recent reports have demonstrated the potential of LAS in selected breast surgery cases [3-5]. We aimed to evaluate the feasibility of systematically performing BCS under LAS in a high-volume breast cancer center. Methods: We conducted a retrospective study including all patients who underwent BCS ± axillary surgery from September 2021 to December 2023 in our institution. Patients operated under GA during the initial period (Sept 2021-March 2022) were compared to those under LAS (June 2022-Dec 2023), excluding the transition phase. LAS combined intravenous sedation (midazolam, dexmedetomidine, ketamine, remifentanil) with local infiltration (naropeine, lidocaine with epinephrine, saline). Feasibility endpoints included conversion to GA, intraoperative tolerance, and early surgical complications. Results: Of the 948 BCS procedures performed during the study period, 708 (75%) were carried out under LAS. Among the eligible patients during the LAS period, 12 refused local anesthesia and were operated under GA. Only 2 conversions to GA occurred during LAS procedures (0.3%), confirming excellent feasibility. We planned more preoperative wire in the LAS group (80% vs. 59%) because of the aqueous environment making small lesions more difficult to feel. Re-operation rates (for positive margins, hematoma, or infection) did not differ between LAS and GA groups (11% in LAS group vs. 13% in GA group, p=0.34). Axillary procedures were performed in both groups (52% in LAS group and 58% in GA group, n=0.06). Oncoplastic techniques were successfully performed under LAS without compromising safety or outcomes. Conclusions: Our results confirm that systematic BCS under LAS is feasible, safe, and applicable to a wide range of breast surgical procedures, including oncoplastic and axillary surgeries. To our knowledge, this represents the largest reported single-center series of breast-conserving surgery performed under LAS, supporting its broader implementation in routine clinical practice and perioperative optimization strategies.

Abstract Background: In patients with clinically node-positive breast cancer undergoing chemotherapy, sentinel lymph node biopsy has been associated with a false-negative rate up to 14% according to previous studies. However, when target axillary dissection techniques, such as the placement of clips or markers in biopsy-proven metastatic lymph nodes, are employed, false-negative rates have been reported to decrease dramatically to approximately 1.4%, as shown in a pivotal study published in 2016. Despite this evidence, there has been no large-scale evaluation of axillary lymph node targeting methods in Korean clinical setting. This study aims to establish foundational data for targeted axillary strategies in Korea by comparing different localization methods used in patients with initially node-positive breast cancer. Methods: This study was conducted as a retrospective multicenter study involving patients with biopsy-proven node-positive breast cancer, who underwent surgery between January 2015 and June 2024. Patients were enrolled from seven institutions based on the following inclusion criteria; primary unilateral breast cancer, clinical tumor stage cT1-T4, biopsy-proven metastatic axillary lymph node with marker placement, and age over 18 years. Detailed analyses were conducted regarding the extent of axillary surgery, the type of marker used (clip or tattoo), and the use of localization techniques such as wire localization. Results: A total of 331 patients were included and the mean age was 49.3 years with 31 months of median follow-up. According to marking methods, targeted lymph nodes were successfully identified in 127 out of 145 patients (87.6%) who received clip markers, and in 178 out of 184 patients (96.7%) who underwent tattoo marking. There were no significant differences in concordance between sentinel lymph node and targeted lymph node across the clip and tattoo group (66.2% vs. 79.3%, p=0.298). Discordance between the sentinel lymph node and targeted lymph node was observed in 12.1% of total patients, 13.8% of patients in the clip marker group and 10.9% in the tattoo marker group. Among the clip group, patients who underwent wire localization showed a non-significant trend toward lower concordance between sentinel lymph node and targeted lymph node compared to those without wire localization (66.7% vs. 83.3%, p=0.069). Demographics and treatment characteristics, including tumor stage, surgery type, and systemic therapy, did not differ significantly between different markers. Conclusions: This is the first multicenter analysis in Korea focusing on targeting methods for metastatic axillary lymph nodes. No significant difference was observed in sentinel lymph node-targeted lymph node concordance and targeted lymph node detection between the clip and tattoo marker groups, suggesting that both methods have comparable feasibility in planning targeted axillary surgery. Interestingly, tattoo-based marking was used at a frequency comparable to clip marking, which contrasts with global trends. This may be attributed to the limited use of clip markers in Korea due to reimbursement restrictions. Also, these findings are clinically meaningful when considered in the context of the well-established false-negative rate of approximately 14% reported in node-positive breast cancer patients undergoing sentinel lymph node biopsy, suggesting that appropriate lymph node targeting strategies may help reduce discordance and improve surgical accuracy. Citation Format: C. Lee, J. Ryu, S. Ahn, J. Lee, H. Shin, J. Lee, Y. Kwak, H. Lee, S. Nam, S. Kim, J. Lee, J. Yu, B. Chae, S. Lee, W. Park, K. Kim, S. Lee. Evaluation of different methods of targeting axillary lymph node for axillary surgery in patients with clinically node-positive breast cancer: A retrospective multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-01-12.

Abstract Background: Breast cancer-related lymphedema (BCRL) remains a persistent and impactful morbidity associated with axillary surgery. Even with sentinel lymph node biopsy (SLNB), the reported incidence of BCRL is 5-7%. As surgical oncology shifts toward minimizing treatment-related morbidity—particularly in patients with clinically node-negative, early-stage breast cancer—techniques that reduce the risk of BCRL are increasingly valuable. Large trials such as SOUND and INSEMA support de-escalation of axillary surgery, demonstrating that SLNB may be safely omitted in select low-risk patients. These findings reinforce efforts to refine surgical techniques for those who still require axillary staging. Technique: We propose a novel, broadly applicable surgical approach: lymphatic-sparing sentinel lymph node biopsy (LSSNBX). This technique preserves and reapproximates the afferent and efferent lymphatic channels after sentinel node excision to facilitate lymphangiogenesis and reduce postoperative lymphedema risk. Unlike axillary reverse mapping (ARM)-dependent approaches, LSSNBX avoids additional mapping procedures, making it more feasible in varied practice settings. The procedure begins with dual-agent mapping (Technetium-99m, indocyanine green [ICG], or blue dye). After identification of the sentinel lymph node, an axillary crease incision is used to access the node. During excision, the afferent and efferent lymphatic bundles are carefully preserved and prevented from retracting. These lymphatic channels are then reapproximated using an absorbable suture, promoting potential reconnection and continuity of lymphatic flow. Importantly, this method simplifies prior ARM-based strategies by performing lymphatic preservation routinely, regardless of ARM findings. Results: A retrospective review at our institution included 103 patients: 52 underwent LSSNBX and 51 underwent standard SLNB without lymphatic preservation. Patient demographics indicated the LSSNBX group was older and had a lower mean BMI. At three-month follow-up using bioimpedance spectroscopy (SOZO®), no cases of BCRL were identified in either group. Notably, the LSSNBX technique added minimal operative time and required no specialized equipment, supporting its feasibility and cost-effectiveness. Conclusion: LSSNBX is a safe, simple, and scalable modification of standard SLNB that aligns with the current movement toward minimally invasive, morbidity-reducing surgical oncology. By preserving and reapproximating lymphatic channels intraoperatively, this technique may reduce the incidence of BCRL and improve long-term patient quality of life. As axillary surgery continues to evolve, the LSSNBX technique represents a promising step in optimizing outcomes. Further studies with larger cohorts and extended follow-up are warranted to validate these preliminary findings. Citation Format: E. Kohilakis, S. Chow, N. Habboosh, M. Bajwa, M. McEvoy, S. Feldman. Lymphatic-sparing sentinel lymph node biopsy to prevent breast cancer-related lymphedema [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-26.

Abstract Objective: To evaluate whether the omission of axillary surgery impacts clinical outcomes in patients with early-stage breastcancer and clinically negative lymph nodes. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing no axillarysurgery with standard axillary interventions (sentinel lymph node biopsy [SLNB] or axillary dissection [AD]). This study followed PRISMA guidelines and was registered in PROSPERO (CRD420250653779). Searches were conducted in PubMed,Web of Science, and Embase through June 2025. Outcomes assessed included overall survival (OS), disease-free survival (DFS),and axillary recurrence (AR). Meta-analyses were performed using RevMan 5.4. Risk of bias was assessed using the RoB 2 tool. Results: Out of 853 records, seven RCTs including 8,806 patients met the inclusion criteria. Among them, 2,915 patients underwent no axillary surgery, while 5,891 received surgical axillary treatment. Two trials compared no surgery with SLNB, and five compared no surgery with AD. No significant differences were found in OS (OR = 1.02; 95% CI, 0.86-1.20; p = 0.84; I2 =36%) or DFS (OR = 0.80; 95% CI, 0.63-1.00; p = 0.05; I2 = 63%). AR was significantly lower in the axillary surgery group (OR= 0.18; 95% CI, 0.10-0.31; p &amp;lt; 0.01; I2 = 39%). Conclusion: The omission of axillary surgery in early-stage breast cancer with clinically negative lymph nodes does not negatively impact overall or disease-free survival. However, it is associated with a higher—though still low—risk of axillary recurrence. Citation Format: B. B. Castelo, L. O. Brito, R. Z. Torresan, C. Cardoso Filho, G. M. Duarte. Omission of Axillary Surgery in Early Breast Cancer with Negative Lymph Nodes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-27.

Abstract Background: Metastasis to the internal mammary lymph nodes (IMLN) plays a critical role in the regional staging and prognosis of breast cancer. Although IMLN involvement often occurs alongside axillary lymph node (AXLN) metastasis, isolated IMLN metastasis without axillary involvement (cN2b) is rare, and the optimal surgical approach for these patients remains uncertain. While axillary lymph node dissection (ALND) is generally recommended for node-positive disease, its necessity in cases of cN2b is debatable. This study aims to clarify the prognostic significance of AXLN status and to assess whether ALND can be safely omitted in breast cancer patients presenting with isolated IMLN metastasis. Methods: We retrospectively analyzed patients with IMLN metastases confirmed preoperatively by cytology, who underwent surgery at our institution between 2007 and 2021. Inclusion required cytological confirmation of IMLN metastasis. Exclusion criteria included clinical T4 tumors, supraclavicular or distant metastases, and bilateral breast cancer. Patients were stratified into two groups: cN2b (isolated IMLN metastasis, n=21) and cN3b (IMLN with AXLN metastasis, n=104). Clinicopathological characteristics and 5-year disease-free survival (DFS) were compared between groups. In the cN2b cohort, oncologic outcomes were further evaluated according to the type of axillary surgery performed: sentinel lymph node biopsy (SLNB) alone versus ALND. Results: Of 15,231 surgically treated breast cancer patients, 230 had IMLN metastasis. After exclusions, 125 (0.8%) were included: 21 (0.1%) with cN2b and 104 (0.7%) with cN3b. The median follow-up was 59 months. The cN2b group demonstrated a significantly higher frequency of medial tumor location (52% vs. 30%, p=0.046) and tended to present with smaller tumor size compared to the cN3b group (p=0.039). Histologically, invasive ductal carcinoma was the predominant subtype in both groups. Hormone receptor-positive tumors accounted for the majority of cases in both cN2b and cN3b groups (62% and 60%, respectively, p=0.85). HER2-positive tumors were seen in 19% of cN2b and 26% of cN3b cases (p=0.50). The 5-year DFS was significantly better in cN2b patients compared to cN3b (94.7% vs. 64.0%, p=0.0049), indicating favorable prognosis in the absence of axillary involvement. Among cN2b patients, 10 underwent SLNB alone and 10 underwent ALND. The remaining patient did not undergo any axillary surgery due to personal preference. DFS rates did not significantly differ between these subgroups (88.9% for SLNB vs. 100% for ALND, p=0.32). In the cN2b group, 20 patients (95.2%), and in the cN3b group, 101 patients (97.1%) received postoperative radiotherapy, with irradiation fields including the regional lymph node areas in all cases. One SLNB-only patient developed distant bone metastasis, but no regional axillary recurrence occurred in any group. Two ALND patients had previously undetected axillary metastases though it is unclear whether these findings had any effect on DFS. Conclusions: This study suggests that breast cancer patients with isolated IMLN metastasis and no axillary involvement (cN2b) have significantly better outcomes than those with combined IMLN and AXLN metastasis (cN3b). Furthermore, omission of ALND in cN2b cases may be feasible and did not appear to compromise disease control, with no locoregional failures observed in the SLNB-only group. These findings support the potential safety and efficacy of a less invasive axillary management strategy—SLNB alone—for appropriately selected cN2b patients. Considering the rarity of this clinical subset, larger prospective studies are warranted to further validate these findings and refine treatment guidelines for isolated IMLN metastasis. Citation Format: Y. Ishizaka, T. Sakai, M. Kasahara, M. Kai, A. Kanazawa, E. Taniguchi, Y. Ito, Y. Kimura, U. Nakadaira, Y. Inoue, T. Maeda, N. Yamashita, A. Kataoka, N. Uehiro, T. Ueno. Evaluating Prognosis According to Axillary Surgery in Breast Cancer Patients with Isolated Internal Mammary Lymph Node Metastasis (cN2b): A Retrospective Cohort Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-29.

Abstract Background: Accurate targeting of axillary lymph nodes (ALNs) is important in breast cancer surgery, especially in patients with ALNs metastasis. Conventional methods such as charcoal tattooing, needle localization, clips or skin marking with ultrasound have significant limitations: incorrect targeting, rapid dispersion, irreversible pigmentation, or dislocation, complicating precise localization. LuminoMark, a novel near-infrared fluorescence (NIRF) imaging agent combining indocyanine green (ICG) with a dispersion-limiting polymer, offers real-time visualization of ALNs without staining or dislocation risk. Methods: This multicenter, prospective study aims to evaluate the safety and efficacy of LuminoMark compared to standard ALN-targeting methods (charcoal tattooing, needle localization, and ultrasound-guided skin marking). The study includes 330 breast cancer patients (165 per group), including those undergoing upfront surgery or surgery following neoadjuvant chemotherapy. The experimental group receives a 0.2-mL subcutaneous injection of LuminoMark into pathologically confirmed metastatic ALNs prior to surgery, while the control group follows institutional standard targeting procedures. The primary outcome is the successful detection rate of the targeted lymph node and check-up of adverse events, and secondary outcomes include time from incision to node detection, total axillary surgical time, postoperative complications, and correlation with sentinel lymph nodes. A prior Phase 2 trial showed no adverse drug reactions or significant differences in efficacy between doses of LuminoMark® and charcoal. A preliminary study involving 13 patients demonstrated a 100% detection rate with LuminoMark® compared to 92.3% with charcoal, with superior intraoperative visualization and no adverse events. The inclusion criteria include women aged 20-70 with invasive breast cancer and clinically/pathologically confirmed ALN metastasis. Exclusion criteria include stage IV disease, pregnancy, history of allergic reactions to the study drug, or inability to comply with study protocols. All participants undergo postoperative monitoring for 48 hours for safety evaluation. Randomization will be performed preoperatively in upfront surgery cases, or after neoadjuvant chemotherapy in neoadjuvant treatment cases. All procedures adhere to NCCN guidelines, which recommend excision of targeted ALNs. In a real comparative study, if LuminoMark® (100% detection rate) is set as experimental group and the various conventional methods (approximately 89.7%) is set as control group, approximately 1,480 subjects are required for each group. However, this study is composed as pilot study including only 10% of the actual required sample size, and the dropout rate was set to 10%. Therefore, 165 patients (164.4 patients) are needed in each group. Since the control group is composed of methods currently being implemented in each institution (charcoal dyeing, needle positioning, ultrasound-guided skin marking, etc.), the number of patients for each method is expected to be different. However, to configure the ratio as close to 1:1:1 as possible, the number of cases will be assigned differently for each institution. This study seeks to confirm its utility in a clinical setting and support future large-scale trials to establish LuminoMark as a feasible material in targeting ALNs for breast cancer surgery. The full protocol of this study was registered in clinicaltrial.gov (NCT06903429). Citation Format: J. Lee, H. Park, B. Kang, J. Moon, Y. Chae, L. Soo Jung, L. In Hee, J. Park, N. Park, E. Kim, S. Jeong, J. Kang, J. Yang, Y. Lim, T. Jung. A prospective, multicenter comparative pilot study to evaluate targeting axillary lymph node surgery for patients with clinically node-positive breast cancer (LUCAS study, KBCSG36) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-06.

Abstract Background: Sentinel node biopsy (SNB) has been the standard of care for patients with clinically node-negative breast cancer (BC) since the 2000s. Recent ASCO guidelines now permit SNB to be omitted under specific conditions in clinical T1N0 BC. While axillary lymph node dissection (ALND) remains a regional control option for early BC, optimal axillary management, including repeat SNB, for ipsilateral breast tumor recurrence (IBTR) remains undefined. To address this, the Japanese Society for Sentinel Node Navigation Surgery (SNNS), established in 1999 to advance sentinel node research in solid tumors, conducted a retrospective cohort study (UMIN No. 000049737) on axillary management in IBTR cases. Patients and Methods: We included patients with clinical Tis-4N0 BC who underwent partial mastectomy and SNB, and whose IBTR was diagnosed between January 2010 and August 2022. Exclusion criteria included clinically node-positive BC, bilateral BC, and stage IV BC. Adjuvant therapy decisions were at the physician's discretion. We analyzed clinicopathological data, focusing on lymphatic mapping and repeat SNB, from primary BC and IBTR medical records. This study received approval from the Kyorin University School of Medicine institutional review board. Results: Our study enrolled 314 eligible cases from 20 Japanese institutions. At primary BC diagnosis, 66 cases were stage 0, 178 were stage IA/B, 66 were stage IIA/B, 1 was stage IIIA, and 3 had unknown stages. SNB was successful in 312 cases (99.3%), with only 12 cases (3.8%) showing positive sentinel lymph nodes (SLN). Breast and regional nodal irradiation were performed in 237 and 8 cases, respectively. IBTR was diagnosed between 3 and 259 months (median: 70 months) after primary BC surgery. Total mastectomy was planned for 243 cases, and partial mastectomy for 64. Sixteen cases also underwent breast reconstruction. Repeat SNB was performed in 216 cases (68.7%), with successful SLN identification in 181 (83.7%). Of the 168 cases that underwent radioisotope-guided lymphatic mapping, hot spots were visualized in 112 (66.6%) via lymphoscintigraphy. SLN localization showed 175 in the ipsilateral axilla, 6 in the contralateral axilla, and 4 in the ipsilateral internal mammary lesion. Positive SLN rates were 9.1% (11 cases) for ipsilateral axilla, 1.6% (1 case) for contralateral axilla, and 0% (0 cases) for ipsilateral internal mammary lesion. Following axillary management for IBTR, repeat SNB was performed in 194 cases (61.7%), lymph node sampling in 2 (0.6%), ALND in 37 (11.7%), and no axillary surgery in 81 (25.7%). Post-IBTR axillary management, 20 cases experienced regional or contralateral lymph node recurrence, and 23 cases died. Conclusion: Repeat SNB is feasible and provides valuable information for de-escalation surgery in IBTR cases. However, axillary management should be carefully considered, taking into account both loco-regional and systemic dissemination at the time of IBTR diagnosis. Citation Format: T. Nakayama, R. Nakamura, T. Onishi, H. Yasojima, J. Ando, H. Jinno, T. Ogawa, T. Aihara, H. Matsumoto, N. Masuda, M. Kawada, S. Kuba, Y. Shinden, N. Wada, M. Kitada, M. Saito-Oba, J. Sakamoto, S. Imoto. A retrospective cohort study on axilla management in ipsilateral breast tumor recurrence after partial mastectomy with sentinel node biopsy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-01-27.

Abstract Introduction: Sentinel lymph node dissection (SLND) omission after neoadjuvant therapy (NAT) in early-stage breast cancer has not yet been studied, because most SLND omission trials do not allow recruitment of patients who undergo NAT. The VENUS trial (ClinicalTrials.gov NCT05315154, ReBEC RBR-8g6jbf, Ethics approved: CAAE:06805118.2.0000.5404) is an ongoing study that aims to evaluate the safety of omitting sentinel lymph node dissection in clinically and ultrasound node-negative early breast cancer (BC). The trial permits neoadjuvant treatment (NAT). Objectives: Evaluate the characteristics of patients enrolled in the VENUS trial until September 25th 2025, who underwent NAT and compare them to the other patients enrolled, in order to determine if it is safe to maintain the recruitment of women with early-stage breast cancer and neoadjuvant treatment indication. Methods: Descriptive interim exploratory analysis of the patients enrolled on the VENUS trial until September 25th 2025. The VENUS trial is a multicenter, prospective, non-inferiority, phase 3 clinical trial that includes women with T1/T2, N0 (clinical/ultrasound), M0 breast cancer, randomized to SLND or no axillary surgery (NAS). Initial treatment could be NAT or upfront surgery, and the axillary ultrasound must be negative before and after the neoadjuvant treatment (analysis groups: NAT-SLND, NAT-NAS, up-front-SLND, up-front-NAS). This interim analysis focuses on patient and tumor characteristics, SLND positivity, and axillary recurrence. Results: So far, 788 women were enrolled, with 287 randomized to SLND and 273 to NAS. Patients' epidemiological characteristics (body mass index, race and menopausal status) were similar in all randomization groups, but those who underwent NAT were younger (NAT-SLND and NAT-NAS mean ages were 53.4 and 53.7 years old versus up-front-SLND and up-front-NAS of 59.7 and 62.7 years old, p=0.01). Among all randomized patients, 45 (8%) underwent NAT, of which 25 had SLND performed and 20 no axillary surgery. They had more aggressive tumor profiles (37.7% HER2 positive tumors and 33.3% triple-negative tumors) and tumors' mean size of 28 mm. SLND positivity seems to be lower after NAT compared to upfront surgery (4.2% vs. 19.9%, p=0.1048), though this difference did not reach statistical significance. No axillary recurrences were observed during the 22-month follow-up. Conclusions: This interim analysis suggests that SLND positivity is lower after NAT and that omitting SLND in this context may be oncologically safe, with no axillary recurrences observed over 22 months of follow-up. However, the small NAT sample limits statistical power, and continued data collection is needed to confirm safety and feasibility. At this stage, continuing the inclusion of patients with indication for NAT in the VENUS trial appears justified. Recruitment will proceed through December 2025. Citation Format: M. P. L. Kraft, G. M. Duarte, D. M. Araújo, R. M. Jales, J. Y. Shinzato, R. Z. Torresan, C. Cardoso Filho, F. P. Brenelli, S. B. Esteves, H. K. Mantovani, G. M. Tavares, A. S. Detoni, E. C. Pessoa, C. K. C. Pessoa, I. de Oliveira Júnior, R. Freitas Júnior, R. M. S. Rahal, V. M. Budel, L. R. Budel, A. P. S. Damin, L. R. Soares, R. D. J. A. de Andrade, F. P. Cavalcante, M. Antonini, R. S. Machado, D. L. Ferreira Filho, K. B. F. Diocesano, S. Vieira, A. Mattar, T. Giuzio, L. Z. Sarian. Omitting Sentinel Lymph Node Dissection After Neoadjuvant Treatment in Early Breast Cancer: Interim Results from the VENUS Randomized Clinical Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-14.

Abstract BACKGROUND: Approximately 20% of women with breast cancer will be node-positive at presentation. In the UK, all patients with newly diagnosed breast cancer have axillary staging with an axillary USS +/- biopsy of abnormal/equivocal nodes and currently UK NICE guidelines recommend axillary node clearance (ANC) for all patients with biopsy proven node positive breast cancer having primary surgery, irrespective of the number of nodes involved. This highly morbid procedure leads to life-long complications in 1 in 3 patients including lymphoedema and chronic pain which dramatically impact quality of life. ANC aims to reduce locoregional recurrence (LRR) and improve breast cancer survival but there is no evidence to support these benefits for patients with limited nodal involvement (cN0, radiologically detected disease). These patients would meet the criteria for omission of ANC based on eligibility for the ACOSOG Z0011 trial, but this approach has not been adopted in the UK due to concerns regarding false negative sentinel node biopsy (SNB) in node positive patients. Targeted axillary dissection (TAD) which combines removal of the localised biopsy proven involved node(s) in combination with a SNB may offer an alternative to ANC, effectively addressing concerns regarding false negative rates while reducing the risk of life-changing complications. The TADPOLE study aims to determine if TAD is a clinically and cost-effective alternative to ANC in patients with low volume node positive breast cancer having primary surgery. METHODS: TADPOLE is a multicentre pragmatic phase 3 randomised controlled trial comparing TAD and ANC in breast cancer patients with low volume nodal disease having primary surgery. All patients with cN0 biopsy proven low volume axillary nodal disease will be eligible to participate. Excluded will be patients with &amp;gt;3 nodes on USS, those who have recurrent disease, previous axillary surgery or neoadjuvant systemic therapy. Participants will be randomised 2:1 to TAD or ANC. Surgical quality assurance (QA) processes will promote standardised introduction of ‘primary’ TAD in the UK and ensure procedure fidelity within the trial. Participants will have adjuvant therapy as per standard of care but axillary radiotherapy (ART) will be prohibited in the TAD group. Robust radiotherapy quality assurance (RTTQA) will be embedded throughout. The co-primary end-points are: i) Patient reported and objective lymphoedema at 12 months ii) Single arm analysis of LRR at 5 years in the TAD cohort. Recruitment of 390 patients in the TAD arm will be required to detect a 50% reduction in lymphoedema at 12 months with 90% power and a type 1 error of 5% and exclude an undesirable LRR of &amp;lt;5% in the TAD cohort at 5 years with one sided 2.5% alpha and 90% power. Inflating for multiplicity and allowing for 5% dropout and 5% crossover a total of 861 patients (574 TAD:287 ANC) will be required for the trial. 40 UK breast units will recruit to the trial. An embedded qualitative study will optimise recruitment and a SWAT (study within a trial) will optimise recruitment of non-English speaking participants. RESULTS: Consensus work to agree how to axillary surgery including primary TAD should be performed has been completed and will underpin the surgical QA within TADPOLE. The trial will commence recruitment September 2025 and include a 9 month internal pilot phase. Recruitment is planned for 28 months with a target of 1 participant/centre/m at 40 sites. CONCLUSION: TADPOLE will address the top UK breast surgery research priority identified in the James Lind Alliance Priority Setting Process. If TAD causes less lymphoedema and is oncologically safe, TADPOLE will change practice, improving outcomes for thousands of patients with node positive breast cancer each year. Citation Format: S. Potter, K. Avery, P. Baji, I. Bhattacharya, N. Blencowe, L. Culliford, R. Cutress, L. Dabner, D. Dodwell, K. Fairhurst, J. Frost, J. Harris, E. Marques, H. Markham, A. Morgan, M. Perkins, S. Rees, K. Roberts, T. Robinson, N. Sharma, S. McIntosh. Targeted axillary dissection vs axillary node clearance in patients with positive axillary nodes in early breast cancer: a multicentre, pragmatic, phase 3 randomised controlled trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-15.

Abstract Objectives: Over the last decade, axillary management strategies for patients with breast cancer have experienced several paradigm shifts toward surgical de-escalation, especially in exceptional responders who have achieved a complete response after neoadjuvant systemic therapy (NST). Current trends in axillary surgery for breast cancer patients who achieved clinical complete response (cCR) to neoadjuvant systemic therapy (NST) are unknown. Methods: In this retrospective cohort study, female patients diagnosed with breast cancer who achieved cCR after NST were selected from the Surveillance, Epidemiology, and End Results database (2010-2021). The proportions of patients undergoing each axillary treatment approach were summarized by year of diagnosis to assess the trend of axillary management strategy. The Cox proportional hazard models with the inverse probability of weighting (IPW) were used to evaluate the effects of axillary surgery on overall survival (OS) and disease-specific survival (DSS). A multivariate logistic regression model was used to explore factors associated with axillary pathological (p)CR. Results: In total, 15,111 patients were included. The nodal positivity rate after NST in cCR patients with initially clinical node-negative breast cancer was only 0.56%, while the nodal negativity rate after NST in cCR patients with initially clinical node-positive breast cancer was 49.57%. Between 2010 and 2021, axillary lymph node dissection (ALND) rates decreased from 55.27% to 29.07% while sentinel lymph node biopsy (SLNB) rates increased from 41.04% to 64.84%. From 2010 to 2021, the percentage of patients with initially node-negative disease receiving ALND after NST decreased from 32.92% to 13.03%, whereas those receiving SLNB increased from 66.24% to 80.82%. Patients who received ALND had worse OS than those who received SLNB (hazard ratio [HR] = 1.662, 95% confidence interval [CI], 1.339-2.063, P &amp;lt; .001). After applying the inverse probability weighting (IPW), patients in the ALND group still had a worse OS than those in the SLNB group (HR = 1.491, 95%CI, 1.164-1.911, P &amp;lt; .001). Meanwhile, patients who received ALND were associated with worse DSS than those who received SLNB (HR = 1.909, 95%CI, 1.485-2.453, P &amp;lt; .001). Despite the application of IPW, the DSS of patients in the ALND group remained inferior to that of the SLNB group (HR = 1.654, 95%CI, 1.243-2.202, P &amp;lt; .001). The logistic regression analysis revealed that initial cN0 was a strong predictor of axillary pCR. Patients who were initially diagnosed with N1 (OR, 0.024; 95% CI, 0.022-0.027), N2 (OR, 0.036; 95% CI, 0.029-0.043), and N3 (OR, 0.028; 95% CI, 0.023-0.034) stages had a decreased odds of achieving axillary pCR. Conclusions: In summary, the results of this study indicated that ALND was administered to up to 13% of patients with originally node-negative breast cancer who achieved cCR following NST. Compared to SLNB, ALND may reduce the survival of patients who obtained nodal pCR, indicating potential overtreatment. In this subgroup of patients, we recommend carrying out SLNB first to determine the node status before the decision to undergo ALND. Citation Format: Y. Zheng, Y. Chen, E. Xia, O. Wang. Trends in axillary surgical strategies for breast cancer patients with clinical complete response after neoadjuvant systemic therapy: a population-based retrospective cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-21.

Abstract Background: The optimal management of the axilla following neoadjuvant chemotherapy (NAC) for initially node-positive breast cancer (cN+) remains contentious, although there has been a trend towards de-escalating morbid axillary surgery under certain conditions. Clinically node-positive breast cancer that converts to node-negative (ypN0) following NAC is increasingly being managed by sentinel lymph node biopsy (SLNB) alone rather than by axillary lymph node dissection (ALND). Recent consensus by experts in St. Galen [Ditsch et al, 2025] suggest SLNB alone may also be acceptable for low volume residual axillary nodal disease (ypN1) following NAC, although data to support the oncologic safety of this approach are limited. The aim of this meta-analysis was to evaluate the long-term oncologic outcomes of SLNB alone for residual axillary nodal disease following NAC. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Medline (Ovid), Embase, and Cochrane Central Registry were systematically searched for studies comparing women undergoing SLNB or ALND following NAC for initially clinically node-positive breast cancer (cN+). Included studies reported one of the following outcomes: axillary recurrence (AR), locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS) or overall survival (OS). A random effects meta-analysis was used to calculate weighted pooled effect estimates (risk ratios, RR) for all outcomes, comparing SLNB alone with ALND for patients with residual nodal disease (cN+/ypN+). Variability across studies due to heterogeneity was estimated using I 2 statistics. Results: Fourteen observational studies were eligible for meta-analysis, providing data for 9,518 patients. The median age of the women included in the studies ranged from 47 to 53 years. Seven studies included only cN1 cases (pre-NAC), with 8 studies reporting outcomes for only ypN1 cases. The median number of sentinel lymph nodes retrieved in each study ranged from 2 to 6. The median follow-up time ranged from 28 to 108 months. The rates of axillary recurrence ranged from 0.2% to 7.8% across all included studies. Distant recurrence rates ranged from 15.7% to 38.6%. No significant differences were observed in AR between patients undergoing SLNB alone versus ALND following NAC: pooled RR 1.12 (95% CI: 0.72-1.74, I 2 =0.0%). Similarly, no significant differences were observed in LRR (RR 0.97, 95% CI: 0.68-1.37, I 2 =0.0%) nor overall mortality (RR 0.96, 95% CI: 0.65-1.42, I 2 =58.3%) between the two groups. However, the pooled risk of distant recurrence was lower for SLNB alone compared to the ALND group (RR 0.75, 95% CI: 0.60-0.95, I 2 =0.0%). Conclusions: This meta-analysis suggests that long-term outcomes of SLNB alone for breast cancer with residual axillary nodal disease following NAC are not inferior to those of ALND. AR rates were low across all included studies; the majority of recurrences were distant, questioning the need for aggressive axillary surgery for patients with low volume residual nodal disease. We await prospective data from several randomized clinical trials, including Alliance A011202 and MAC 19, to further guide axillary management in this group of patients.

Abstract Background: The indications for and extent of axillary surgery in breast cancer have evolved significantly over the past two decades and remain an area of active research and debate. Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in patients with early-stage breast cancer. However, emerging data suggest that axillary surgery may be safely omitted in select patients aged ≥60 years with early-stage, luminal A, clinically node-negative breast cancer. This prospective study aimed to assess the applicability of this strategy in patients with hormone receptor-positive (HR+), HER2-negative (HER2−) tumors. Method: This prospective study included 100 patients diagnosed with cT1-2N0M0, HR+HER2- breast cancer (BC) who underwent combined treatment from 2023 to 2025 at the FSBI «N.N. Petrov National Medical Research Center of Oncology» of the Russian Ministry of Health. All patients had clinically negative axillary lymph nodes confirmed via ultrasound, mammography and mammoscintigraphy/breast molecular imaging with 99mTc-MIBI. Surgical axillary staging was omitted in this patient population. Preoperative sentinel lymph node localization for adjuvant radiation treatment planning was performed using single-photon emission computed tomography (SPECT) lymphoscintigraphy. Results: Among 100 patients with cT1-2N0M0 HR+HER2- breast cancer median age was 67 [59; 86] years. Median tumor size was 15 [4; 30] mm and tumors were grade 1 or 2. Estrogen receptor (ER) expression ranged from 90-100% in 95 cases and 70-80% in 5 cases. Progesterone receptor (PR) expression was 0-10% in 17 cases, 20-40% in 4, and 60-100% in 79. The Ki-67 proliferation index was 1-10% in 29 cases, 11-20% in 46, and 21-30% in 25. Histological subtypes included 94 cases of invasive carcinoma of no special type (NST), 3 - lobular carcinomas, and 3 - mucinous carcinomas. All patients in the study received adjuvant radiotherapy, administered in hypo- or ultra-hypofractionation regimens at the discretion of the radiation oncologist for breast and sentinel lymph nodes. Specifically, 15 patients received a 5-fraction regimen, 50 patients received 15 fractions, 35 patients received 16 fractions, and 2 patients underwent high-dose brachytherapy additionally. Adjuvant hormone therapy was recommended for all patients: 79 received Aromatase Inhibitors and 21 received Tamoxifen. No patient was recommended to receive adjuvant chemotherapy. Conclusion: We believe that these findings support careful implementation of omission of surgical staging of the axilla in postmenopausal patients with cT1-2N0, HR+HER2− breast cancer and a negative axillary lymph nodes. At our institution, this approach is currently implemented in patients over 59 years of age with ECOG performance status &amp;lt;3, tumor grade 1-2, ER expression &amp;gt;20%, and Ki-67 index &amp;lt;30%. Citation Format: A. O. Gorina, P. V. Krivorotko, A. S. Emelyanov, D. A. Enaldieva, E. K. Zhiltsova, L. P. Gigolaeva, T. T. Tabagua, A. V. Komyakhov, V. V. Mortada, P. S. Pesotsky, D. G. Ulrikh, N. S. Amirov, V. F. Semiglazov. Refusal of sentinel lymph node biopsy in patients with luminal A subtype early breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-08.

Abstract Background: Mammographic screening programmes reduce breast cancer mortality but detect many small good-prognosis tumours which may not progress. Screen-detected cancers are currently treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies are evaluating omission of radiotherapy in low-risk disease. However, there is little evidence for surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of lesions of uncertain malignant potential and benign lesions. SMALL (ISRCTN 12240119) aims to determine the feasibility of using this approach to treat small invasive tumours detected within the UK NHS Breast Screening Programme. Methods: SMALL is a phase III multicentre RCT comparing standard surgery with VAE for screen-detected cancers. Main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomised 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are1. Non-inferiority comparison of the requirement for a second procedure following excision2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019. Recruitment halted in 2020 for 5 months due to COVID-19. At 9th July 2025, 49 centres are open, with 640 patients randomised. The randomisation rate is approximately 45%, and per site recruitment rate is 0.4-0.5 patients/month. Drawing from QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback is ongoing, and wider feedback is being delivered across sites via recruitment training workshops. Patient interviews are ongoing to explore patient views and experiences of the trial. Conclusion: SMALL continues to have excellent recruitment, is expected to complete recruitment in 2026 and have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme award 17/42/32 Citation Format: S. McIntosh, C. Coles, D. Dodwell, K. Elder, B. Elsberger, J. Foster, C. Gaunt, J. Henderson, C. Mabena, J. Morgan, Z. Nabi, I. Lyburn, S. Paramasivan, S. Pinder, S. Pirrie, S. Potter, T. Roberts, N. Sharma, E. Southgate, H. Stobart, A. Talwalkar, S. Taylor-Phillips, W. Teh, E. Turner, M. Wallis, D. Rea. Small: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer - a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-09-12.