Axillary Recurrence Research Articles

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study.

The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor-positive/human epidermal growth factor receptor 2-negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.

The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC. A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation. Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n=353) or TAD alone (n=148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n=2) and 0.8% (n=4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LNof one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence. The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy.

Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) haveexcluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) status (odds ratio [OR] 2.5; p < 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and twoof the three underwent ALND at the initial surgerywith no additional positive nodes. In cT1-2N0 breast cancer, HR+/HER2- status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.

Real-World Implications of the SOUND Trial.

The SOUND trial demonstrated that omission of sentinel lymph node biopsy (SLNB) is noninferior to axillary staging in patients with early-stage breast cancer (BC) and negative axillary ultrasound (AxUS). We examined the generalizability of these findings in patients with hormone receptor (HR)+HER2- disease. Patients with cT1N0M0, HR+HER2- BC and negative AxUS undergoing breast conservation with SLNB from 2016 to 2023 were identified from a prospectively maintained database. Clinicopathologic characteristics, disease burden, adjuvant treatment, and oncologic outcomes were examined and compared with the SLNB arm of the SOUND trial. In postmenopausal patients, the impact of nodal status and 21-gene recurrence score on chemotherapy recommendations were also examined. Of 3972 patients with cT1N0M0 HR+HER2- breast cancer, 544 underwent AxUS; 312 met SOUND eligibility criteria. Median age was 57 (interquartile range [IQR] 48-64) years, and 199 (63.8%) were postmenopausal. Median (IQR) tumor size was 1.3 (0.9-1.7) cm, and 260 (83.3%) tumors were grade 1 or 2. Sentinel lymph node biopsy was positive in 38 (12.2%) patients. Only three (0.4%) had ≥ 4 positive lymph nodes. At a median follow-up of 26.2 (IQR 10.8-38.2) months, there were no axillary recurrences and one (0.3%) distant recurrence. Among postmenopausal women with recurrence score ≤ 25, chemotherapy recommendations were not associated with nodal status. Examination of our real-world HR+ HER2- "SOUND-eligible" population suggests that nodal disease burden and oncologic outcomes are similar to the SOUND trial population, supporting careful implementation of trial results into multidisciplinary practice. In postmenopausal patients, omission of SLNB does not appear to impact adjuvant chemotherapy recommendations.

Excluding Upper Axillary Level 1 in Regional Nodal Irradiation Does Not Increase Axillary Recurrence Risk in Patients With Breast Cancer

PurposeThe optimal extent of regional nodal irradiation (RNI) in postoperative radiotherapy for breast cancer, particularly regarding axillary level 1 (AXL1), remains uncertain. This study aims to compare clinical outcomes between extensive RNI including the entire axilla and limited RNI excluding the upper AXL1 in patients with breast cancer. MethodsA retrospective analysis included 1,780 women with non-metastatic unilateral breast cancer who underwent RNI during postoperative radiotherapy between 2007 and 2018. Patients were classified into extensive and limited RNI groups based on the upper AXL1 inclusion in the radiation field. Propensity score matching yielded a cohort of 1,020 patients. Non-inferiority of limited RNI compared to extensive RNI was assessed with a defined margin of ≤2% in the 5-year axillary recurrence rate. ResultsAfter a median follow-up of 67.9 months, the 5-year axillary recurrence rates were similar between extensive and limited RNI groups (1.2% vs. 1.6%; Plog-rank=0.790). Limited RNI demonstrated non-inferiority with a 0.4% difference (95% confidence interval, -1.1%–1.9%; Pnon-inferiority=0.019). Disease-free survival (87.9% vs. 91.5%; Plog-rank=0.122) and overall survival (94.1% vs. 96.9%; Plog-rank=0.260) at 5 years were not significantly different between extensive and limited RNI groups. Multivariable analysis revealed that lymphovascular invasion (hazard ratio [HR], 5.17; P=0.02) and negative hormone receptor status (HR, 11.73; P=0.002) were associated with a higher risk of axillary recurrence, while limited RNI showed no significant association (HR, 1.35; P=0.652). Subgroup analysis demonstrated that extensive RNI did not improve axillary control in patients with lymphovascular invasion, hormone receptor negativity, positive lymph node metastasis, or a small number of nodes removed. ConclusionLimited RNI, excluding the upper AXL1 from the radiation field, demonstrated axillary recurrence rates comparable to those of extensive RNI in patients with breast cancer. The study suggests that extensive RNI may not provide additional therapeutic benefits, while limited RNI appears to be a valid option for regional control.

ThP2.4 - Unveiling the Odds: Identifying the Axillary Recurrence rates in Invasive Breast Cancer Surgery in a district general hospital - Seventeen years of Surgical Performance decoded

Abstract Introduction Axillary recurrence should be minimised by effective staging and treatment where appropriate Minimum standard &amp;lt;5% axillary recurrence at 5 years Target &amp;lt;3% axillary recurrence at 5 years according to UK ABS guidelines. Methods All patients with primary cancer diagnosed at our institution between January 2004 and December 2020 were identified from a prospectively maintained database of operations obtained from the medical coding department. Demographics of the patients, pre-operative investigations, MDT discussion outcomes, operative details (and complications), post-operative pathology, neo-adjuvant and adjuvant therapy regimens and follow-up data were recorded. All patients were followed up to the censoring date of December 2021 which gave a median follow-up of 18 months (range, 12- 204). Axillary recurrence and treatment regimens were recorded. Primary outcome measures were overall axillary recurrence and disease-free. IBM SPSS Statistics (Version 26.0 (IBM Corporation, Armonk, NY, USA) was used for statistical analysis to determine patient and pre-operative pathological characteristics that were predictive of isolated axillary recurrence after completion of the primary treatment course. Significance was defined as P&amp;lt;0.05. Results There were 4024 women diagnosed with breast cancer in Midyorks trust between this period who were referred and had surgical intervention. Of these, 107 patients were identified with recurrences. 12 were found to have an isolated axillary recurrence (8 ANC 4 SLNB) Conclusion The 17-year isolated axillary recurrence rate of women treated was 0.3%. Multimodality management at the time of recurrence, including axillary surgery, radiation, and systemic therapy, significantly improved the morbidity

SP6.2 - Oncological outcomes following sentinel lymph node biopsy in patients with node positive breast cancer at diagnosis who achieve an axillary pathological complete response to neoadjuvant systemic therapy

Abstract De-escalation of axillary surgery following neoadjuvant chemotherapy (NACT) for patients with node positive breast cancer at diagnosis have focused on ensuring a low false negative rate for those who undergo sentinel lymph node biopsy (SLN) only with limited data to date on oncological outcomes. This study aimed to assess the medium-term oncological outcome in patients who have an axillary pCR following NACT and undergo de-escalation of axillary surgery with only a SLN performed post NACT. A consecutive series of patients with cytologically proven node-positive breast cancer who received NACT and achieved a nodal pCR on SLN between 2013-2021 were retrospectively analysed. Eligible patients underwent an end of treatment axillary ultrasound and if axillary nodes appeared sonographically normal a sentinel node biopsy was performed, with dual modality mapping (radioisotope and blue dye) at the time of breast surgery. The primary outcome of interest was disease free recurrence (DFS), and the secondary outcome was isolated axillary recurrence. 79 patients (median age 48 years) received NACT and had cytologically proven node-positive disease at diagnosis and attained an axillary pathological complete response (pCR) post NACT. The median nodal yield at SLN was 4 (range 1-9). Median follow up was 4.4 years. Only 1 patient experienced an axillary recurrence. Triple negative subtype had the lowest overall DFS. In this cohort, axillary recurrence remains uncommon. The optimal surgical strategy for safe de-escalation of axillary surgery post NACT remains in focus with adjuncts such as nodal marking and targeted axillary currently under study.

Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy.

In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown. Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence. Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09-31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11-19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31-26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence. Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for the prevention of axillary recurrence and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.

Axillary Recurrence in Sentinel Lymph Node Negative Mastectomy Patients at 16 Years Median Follow Up: Natural History in the Absence of Radiation

BackgroundAxillary recurrence following lumpectomy with a negative sentinel lymph node biopsy (SLNB) is rare, possibly due to routine use of whole breast radiation. In this study, we characterized the rate of any axillary recurrence among mastectomy patients with a negative SLNB and no adjuvant radiation therapy. MethodsWe identified women who underwent mastectomy with SLNB for early-stage breast cancer (1999-2005) and included patients with pathologically negative nodes and no axillary dissection or adjuvant radiation. The primary outcome was ipsilateral axillary recurrence. ResultsA total of 234 women, median age 50 years, underwent 242 mastectomies. Histology showed 112 (46%) invasive cancers, 16 (7%) ductal carcinoma in-situ (DCIS) with microinvasion, and 114 (47%) pure DCIS. Cancers were predominantly estrogen receptor positive (59%) and moderate (41%) or high grade (32%). A mean of 2 final sentinel nodes were excised (range 1-6) and 21 patients (9%) had isolated tumor cells on SLNB pathology. At 16 years median follow up (range 1-22 years), 3 patients (1.2%) developed an isolated axillary failure, and 1 had concurrent axillary and chest wall recurrences (total axillary recurrence rate 1.7%). Three of four axillary recurrences occurred in patients with moderate or high-grade estrogen receptor-positive DCIS without invasion on mastectomy histology. Median time to axillary recurrence was 70.5 months (range 29-132 months). ConclusionsAxillary recurrence is rare after a negative SLNB, even in the absence of adjuvant radiation. This supports the safety of forgoing additional surgery or radiation to the axilla in the early-stage breast cancer and a negative SLNB.

Long-Term Oncologic Outcomes of Omitting Axillary Surgery in Breast Cancer Patients with Chest Wall Recurrence after Mastectomy.

The management of the axilla in breast cancer patients with isolated chest wall recurrence (CWR) after mastectomy remains controversial. Although sentinel lymph node biopsy (SLNB) for restaging is feasible, its role is unclear. We aimed to determine if the omission of axillary restaging surgery in female patients with operable presumably isolated CWRs could result in an increased risk of second recurrences. In this retrospective multicentre study, patients who developed CWRs were reviewed. We excluded patients with suspected or concomitant regional/distant metastases, bilateral cancers and patients without CWR surgery. Patients' demographics, pathological data and subsequent recurrences were collected from a prospective database and were compared between patients with axillary lymph node dissection (ALND) and/or SLNB versus no axillary operation at CWR. A total of 194 patients with CWRs were eligible. The median age at CWR was 56.0 (IQR 47.0-67.0) years old. At recurrence, 8 (4.1%), 5 (2.6%) and 181 (93.3%) patients had ALND, SLNB and no axillary operation, respectively. Patients with no axillary surgery during CWR were associated with, at primary cancer, a lower incidence of ductal carcinoma in situ as diagnosis (p = 0.007) and older age (p = 0.022). Subsequent ipsilateral axillary (p = 0.768) and second recurrences (p = 0.061) were not statistically different between patients with and without axillary surgery at CWR on median follow-up of 59.5 (IQR 27.3-105) months. In patients without evidence of concomitant regional or distant metastasis at CWR diagnosis, omission of axillary restaging surgery was not associated with an increased ipsilateral axillary or second recurrences on long-term follow-up.

Axillary management and long-term oncologic outcomes in breast cancer patients with clinical N1 disease treated with neoadjuvant chemotherapy

BackgroundLow false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC.MethodsBC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014–2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed.Results81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70–11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84–35.60, p = 0.006).ConclusionsSLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.

Rectal metastasis arising from breast cancer: a case report.

Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

Prognosis of isolated locoregional recurrence after early breast cancer with immediate breast reconstruction surgery: a retrospective multi‑institutional study.

The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population. This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS). Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS. Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Radiation-Induced Breast Angiosarcoma Associated with Homolateral Axillary Recurrence: A Case Report

Breast angiosarcoma is a rare aggressive tumor that develops from connective tissue of vascular origin with a tendency towards rapid recurrence and the appearance of visceral metastases. It occurs either as a primary tumor in young women or as a secondary tumor following breast irradiation. We report a case of breast angiosarcoma associated with homolateral axillary recurrence in a 45-year-old woman treated for bilateral breast cancer.

Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy – A two center cohort study

BackgroundThe aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). MethodsAll patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). ResultsA total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30–106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6–99.9 %) ConclusionAlthough longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.

Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]

Abstract PO3-06-02: Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study

Abstract Background: Until 2012, breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0(i)) in the sentinel node (SN) received axillary lymph node dissection (ALND). ALND is associated with lymphedema, paresthesia, functional impairment, and pain. In 2012, national Danish guidelines for patients with pN1mi and pN0(i) were changed reflecting several randomized clinical trials showing non-inferior prognosis when ALND was omitted. Since 2012, appr. 450 Danish breast cancer patients have been spared ALND each year. Development of axillary recurrence(AR) from minimal metastatic disease left in the axilla may take longer than experienced after macrometastatic disease. Hence, long-term follow-up is needed to evaluate the safety of omitting ALND for patients with pN1mi and pN0(i). Therefore, we aimed to investigate these outcomes with 10 years of follow-up. Methods: In this national register-based study, we included all women with primary breast cancer surgery between 01.01.2008 and 31.12.2021, who had pN1mi and pN0(i) in the SN. Women treated between 01.01.2008-31.12.2011 had received ALND, while in women treated between 01.01.2012 and 31.12.202,1 ALND was omitted. The two groups were compared with SN-negative patients (pN0) without ALND. The primary outcome was AR, and the secondary outcome was overall survival (OS). Information on surgery, nodal status, and recurrence were retrieved from the national Danish breast cancer group (DBCG) database. The definitions of pN1mi, pN0(i) and pN0 were according to AJCC, 8TH edition. We analyzed patient- and tumor characteristics with descriptive statistics, χ2 and Fisher exact test. The cumulative incidence of AR was calculated. OS was estimated using the Kaplan-Meier method and compared with a log-rank test. The effect of ALND was estimated with a Cox proportional hazards model, adjusting for age at operation, histology, malignancy grade, hormone receptor, HER2 status, and whether they received adjuvant systemic treatment or radiation therapy. With all statistical analysis, a two-tailed α-level of 0.05 was used. Results: 22,790 patients were included in the study. Overall,14.3% had pN1mi, 8.6% had pN0(i) and 77.1% had pN0. Of pN1mi or pN0(i) patients, 1490 had an ALND; 1227 patients with pN1mi and 263 patients with pN0(i). In 3737 patients ALND was omitted: 2036 with pN1mi and 1701 with pN0(i). Regarding the primary outcome, 1.1% of patients with pN1mi or pN0(i) had an AR, while 0.5% of the pN0 patients had AR. Analyzing patients with pN1mi or pN0(i) with or without ALND, 0.2% and 1.5%, respectively, had an AR. In subanalysis of patients with pN1mi with or without ALND, 0.2% and 1.8%, respectively, had an AR. In a subanalysis of patients with pN0(i), no patients with pN0(i) and ALND had an AR, while 1.1% of patients with pN0(i) had an AR when ALND was omitted. OS after 10 years of follow-up for the group of patients with pN1mi or pN0(i) was 81.5%; 83.7% for patients with and 79.12% for patients without ALND. For pN0 patients without ALND OS was 82%. This difference between the three groups was statistically significant(p&amp;lt; 0,01). However, when adjusting for risk factors, there was no statistically significant difference in OS between the patients with pN1mi or pN0(i) with and without ALND (p=0.6). Likewise, no statistically significant difference was found in OS, when looking at the subgroups of pN1mi with or without ALND (p=0.5) and pN0(i) with and without ALND(p=0.41). Conclusion: In this large register-based nationwide study we found a slightly higher rate of AR after 10 years of follow-up in breast cancer patients with micrometastases or isolated tumor cells in the SN if ALND was omitted. However, the axillary recurrence rate was low (&amp;lt; 2%), and after adjusting for other risk factors the increased recurrence rate did not affect OS. These results confirm the safety of omitting ALND in these patients. Citation Format: Riazan Hawaz-ali, Frederikke Munck, Tove Tvedskov, Niels Kroman. Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register 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 PO3-06-02.

Abstract PS01-02: Long-term outcomes of sentinel lymph node biopsy following neoadjuvant chemotherapy for initially node-positive breast cancer: A systematic review and meta-analysis

Abstract Background: Sentinel lymph node biopsy (SLNB) alone is now frequently offered to women with initially node-positive breast cancer who convert to pathologically node negative (nodal pCR) following neoadjuvant chemotherapy (NAC), despite limited long-term data regarding the oncologic safety of this approach. The aim of this meta-analysis was to evaluate the long-term oncologic outcomes associated with SLNB alone following NAC for initially node-positive breast cancer. 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. Included studies reported one of the following outcomes: axillary recurrence (AR), locoregional recurrence (LRR), disease-free survival (DFS) or overall survival. A random effects meta-analysis was used to calculate weighted pooled effect estimates (risk ratios, RR) for all outcomes. Variability across studies due to heterogeneity was estimated using I2 statistics. Subgroup analysis was performed by length of follow-up for each study. Risk of bias within studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Data for participants undergoing treatment between 2004 and 2022 was captured across studies. The median age of women treated with NAC for initially node-positive breast cancer ranged from 46 to 60 years. The median follow-up time ranged from 19.5 to 108 months across included studies. Nine observational studies were eligible for meta-analysis. No studies were excluded from the analysis on the basis of quality: Newcastle-Ottawa Scale scores ranged from 6 to 9 (maximum possible score of 9). Rates of axillary recurrence (AR) were low across all included studies (range 0.0% to 5.6%). For AR, data for 2,882 patients from 7 studies was quantitatively synthesized (SLNB=1,964; ALND=917). For LRR, data for 2,629 patients from 7 studies was quantitatively synthesized (SLNB=1,857; ALND=771). No significant differences were observed in AR between patients undergoing SLNB alone versus ALND following NAC for initially node-positive breast cancer: pooled RR 1.02 (95% CI: 0.46-2.29, I2=0.0%). Similarly, no significant differences were observed in LRR (RR 0.70, 95% CI: 0.45-1.10, I2=0.0%), DFS (RR 0.77, 95% CI: 0.55-1.08, I2=0.0%), nor overall mortality (RR 0.66, 95% CI: 0.33-1.33, I2=0.0%) between the SLNB and ALND groups. Conclusions: Among patients who convert to node-negative following NAC, this meta-analysis suggests that SLNB alone does not result in significantly different oncologic outcomes compared to ALND, and that de-escalation of axillary surgery to SLNB alone in this context may be safely considered in this patient population. Citation Format: Mariam Rana, Anna Weiss, Alison Laws, Carol Mita, Tari King. Long-term outcomes of sentinel lymph node biopsy following neoadjuvant chemotherapy for initially node-positive breast cancer: A systematic review and meta-analysis [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 PS01-02.

Abstract PO4-23-02: Blue Dye-Only for Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Initially Node-positive Breast Cancer

Abstract Importance: Randomized trials evaluated the false negative rate (FNR) of sentinel lymph node biopsy (SLNB) in initially node-positive (cN1/2) breast cancer (BC) patients who downstaged after neoadjuvant chemotherapy (NAC): the studies were negative, as they found FNR above 10%. However, the FNR was adequate when the lymph node was marked with a clip before NAC or at least 3 lymph nodes were removed. SLNB using a combination of blue dye and a radiotracer (Technetium-99) was encouraged to facilitate identification and maximize SLNB results in this scenario. However, radiotracer is unavailable in many services around the world, particularly in low- and middle-income countries (LMIC), but the feasibility and the recurrence rates of SNLB with the use of blue dye-only, in previous cN1/2 patients, are unknown. Objective: The aim of this study was to evaluate the feasibility, proportion of patients undergoing SLNB without axillary dissection (AD) and mean number of resected sentinel nodes (SN), and recurrence rates (axillary recurrence [AR], ipsilateral breast recurrence [IBR], new contralateral primary, disease-free survival [DFS] and overall survival [OS]) of SNLB with the use of blue dye-only in initially node-positive BC (cN1/2). Design, Setting, and Participants: From 2013 to 2023, a cohort of patients undergoing NAC was evaluated at a public institution in Brazil (Hospital Geral de Fortaleza - HGF). Radiotracer and clips were not available. Patients with prior cN1/2 were identified and evaluated. AD was not recommended in cases of negative histopathological results for lymph node metastases after SLNB using blue dye-only. Inflammatory, cN0 and cN3 BC patients were excluded. Results: Among 119 cN1/2 BC patients treated with NAC, 100 (84%) cases underwent SLNB with blue dye-only and 70 (59%) had SLNB alone. The median of SN were 3.1 and 55 (78%) cases had 3 or more SN. No events related to blue dye occurred. The median age of these 70 patients was 49 (25-84) years, and most cases were T2 (n=40/57.1%), followed by T3 (n=18/25.7%), T4 (n=6/8.6%) and T1 (n=6/8.6%), while N1 predominated in axillary status (n=64/91.4%). Regarding breast cancer subtype, there were 19 (27.1%) hormone receptor-positive/HER2-negative, 16 (22.9%) hormone receptor-negative/HER2-positive, 21 (30%) hormone receptor-positive/HER2-positive and 14 (20%) triple-negative cases. 55 (79%) patients received regimens containing anthracyclines and taxanes. Anti-HER2 therapy was used in all cases, but pertuzumab associated with trastuzumab were available in only 8 patients (8/37). Breast-conserving surgery was performed in 40 (57%) cases while total mastectomy in 30 (43%). Patients with hormone-positive BC received endocrine therapy. Adjuvant radiotherapy was made in all cases, except one who underwent mastectomy. After 36 months of median follow-up, no axillary recurrences were observed. One patient had a new primary in the contralateral breast. Three patients had distant disease and two died. Conclusions: This cohort found that the use of SLNB with blue dye-only in Initially cN1/2 BC patients who achieved complete response after NAC is feasible, with very low axillary recurrence rates, like previous reports in the literature that used a combination of tracers. These data reinforce the need for further studies in this scenario, as it maintains the possibility of avoiding AD in places with difficult access to oncological treatment, especially in LMIC. Figure 1 - Flowchart cN: Clinical node stage; BC: Breast cancer; NAC: Neoadjuvant chemotherapy; SNLB: Sentinel lymph node biopsy; AD: Axillary dissection; SN: Sentinel node Table 1 - Demographic Characteristics Citation Format: Francisco Pimentel Cavalcante, Felipe Zerwes, Alessandra Souza, Patricia Ziegelmann, Ryane Alcantara, Amanda Cardoso, Andre Mattar, Eduardo Millen, Antonio Frasson. Blue Dye-Only for Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Initially Node-positive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-02.

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study