Axillary Node Research Articles

A nomogram to predict the risk of axillary upstaging in patients with Z0011-eligible breast cancer.

e12606 Background: ACOSOG Z0011 trial showed that in early cT1-2N0 breast cancer patients with 1-2 positive lymph nodes in sentinel lymph node biopsy (SLNB) can safely omit axillary lymph node dissection (ALND) without compromising local control and long-term survival. Although it is widely accepted worldwide, controversy and concerns remain that the incidence of non-sentinel lymph node metastasis may lead to pathological lymph node (pN) upstaging and insufficient systemic treatment. This study aims to identify risk factors for having ≥4 metastatic lymph node (pN2-3) in patients who met Z0011 criteria and received SLNB. Methods: This is a retrospective study enrolled 733 cT1-2N0 breast cancer patients with 1-2 positive SLNs treated between 2011-2022 at Sun Yat-sen Memorial Hospital. All patients had received SLNB followed by ALND. Patients included were divided into the training and validation sets at a 7:3 ratio. Differences were compared between pN1(1-3 LN+) and pN2-3(≥4 LN+) in training set using either t test or chi-squared test. Multivariate logistic regression was conducted to identify risk factors for pN upstaging and to form the basis of a predictive nomogram. The validation was processed in the other validation set and nomogram performance was evaluated using the area under ROC curve (AUC). Results: Among the 733 patients enrolled, 127 (17.3%) patients had pN upstaging (pN2-3) after ALND. There was a big difference of pN upstaging between the patients with 1 (47/511, 9.2%) and 2 (80/222, 36%) positive SLNs. 488 patients were allocated to the training set, among which 18.2% had pN upstaging. In univariate analysis, pN were differed by cT stage, axillary ultrasound appearance, histological grade, molecular subtype, Ki67, lymph vascular invasion, pathological tumor size, SLN metastasis type (micrometastasis or macrometastasis), positive SLN numbers and negative SLN numbers. Multivariate logistic analysis resulted six independent risk factors associated to pN upstaging: ultrasound suspicious node (OR=1.93; 95% CI: 1.08-3.47), positive lympho-vascular invasion (OR=2.27; 95% CI: 1.25-4.13), larger tumor size (OR=2.07; 95% CI: 1.15-3.73), SLN macro-metastasis (OR= 9.15; 95% CI: 1.07-78.13), two positive SLNs (OR= 6.59; 95% CI:3.70-11.76) and less negative SLN number (OR=1.54; 95% CI: 1.22-1.89). These factors were used to construct a predictive nomogram, exhibiting excellent performance with AUC values of 0.819 and 0.827 in the training and validation cohorts respectively. Conclusions: The Z0011-eligible patients with two positive SLNs may have a high risk of pN upstaging and need to be cautious to spare ALND. A practical nomogram is helpful to identify patients at high risk of pN upstaging and avoid insufficient systemic treatment.

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (OPBC-03/SAKK 23/16/IBCSG 57-18/ABCSG-53/GBG-101-TAXIS).

TPS611 Background: Axillary lymph node dissection (ALND) is standard of care for most patients with clinically node-positive breast cancer (cN+BC), either in the adjuvant setting or in case of residual nodal disease after neoadjuvant chemotherapy (NACT). At least one quarter of patients with breast cancer experience long term morbidity after ALND. The TAXIS trial was designed to investigate if axillary radiotherapy (ART) can replace ALND in patients with cN+ BC who underwent tailored axillary surgery (TAS), which is recognized as one of the most important uncertainties and controversies in axillary management of patients with breast cancer. Methods: To test the remaining indications for ALND in clinical practice, we designed the international, multicenter, phase-III, non-inferiority, randomized controlled TAXIS trial to be pragmatic (average PRECIS-2 score of 4.44). Accordingly, most study domains follow usual care conditions, including eligibility (following routine indications for ALND in clinical practice), surgical skills and techniques, and follow up. The radiation oncology protocol included detailed recommendations and an extensive quality assurance program, which was developed to address the limitations of prior landmark trials and increase acceptability among recruiters. The main objective of the trial is to demonstrate that treatment with TAS and ART is non-inferior to TAS and ALND in terms of disease-free survival (DFS) of patients with cN+ BC detected by imaging or palpation in the upfront surgery setting or in case of residual disease after NACT. Randomization at a 1:1 ratio is mainly performed intraoperatively to either use TAS followed by ALND and regional nodal irradiation excluding the dissected axilla as a target volume (arm A) or to use TAS followed by regional nodal irradiation including the full axilla (arm B). The sample size is based on the primary endpoint DFS. With a type I error of 5% and a power of 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm). The sample size was calculated to be 1500 patients (750 per arm). Enrolment started in July 2018 and will stop after reaching 1500 patients, which is expected to be completed by Q4/2025. With currently 51 active sites from Europe, Canada and Korea within the network of the Oncoplastic Breast Consortium (OPBC), >950 patients were randomized by January 2024. Another 14 sites in Europe, USA, and South America will join the trial in 2024. The interim analysis (after 20% of the required events) is expected for Q4/2024 and will be reviewed by the IDMC. The primary endpoint analysis is planned in Q4/2030. Clinical trial information: NCT03513614 .

Deep learning-based quantitative assessment of tumor-infiltrating lymphocytes from hematoxylin and eosin-stained slides in triple-negative breast cancer: A prognostic study.

553 Background: Tumor-infiltrating lymphocytes (TILs) are pivotal in predicting responses to preoperative chemotherapy in triple-negative breast cancer. Yet, their clinical adoption as a diagnostic marker is limited by the challenge of achieving high accuracy with objective measures. This study introduces a novel AI-based method to quantitatively assess stromal TILs within the tumor bed using hematoxylin and eosin (H&E)-stained slides, examining their correlation with disease-free survival (DFS) and overall survival (OS). Methods: In this study, 68 cases of breast cancer with axillary lymph node metastasis at the time of resection were selected from a total of 3,902 resections conducted between 2002 and 2016. We then developed an AI-based model to detect the epithelium and lymphocytes (CD3/CD20) from H&E-stained slides. This model was trained using annotated datasets, which included 26,509 images of the epithelium and 12,273 images of lymphocytes. The tumor bed areas were precisely defined by pathologists. Subsequently, the AI model identified epithelial and lymphocyte regions within these predefined areas. The TILs score was then calculated as the ratio of the lymphocyte area to the total stromal area within the tumor bed, excluding the epithelial areas identified by the AI model. Finally, we assessed the prognostic significance of the TILs score for DFS and OS through ROC analysis and log-rank tests. Results: ROC analysis identified an optimal TILs score threshold of 0.0042 for both DFS and OS, with an AUC of 0.743 (95% CI, 0.622-0.864) for DFS and 0.686 (95% CI, 0.559-0.812) for OS. This threshold significantly stratified patients into groups with distinct DFS and OS outcomes (P=0.003 and P=0.008, respectively). Conclusions: AI quantification of TILs offers a promising prognostic tool in triple-negative breast cancer, enhancing the objectivity and clinical utility of pathological analyses. Accurate TILs measurement could revolutionize prognostication and treatment planning.

De-escalation neoadjuvant chemotherapy in triple negative breast cancer.

e12520 Background: Neoadjuvant chemotherapy (NAT) represents the predominant therapeutic approach in the early triple negative breast cancer. NAT has demonstrated high overall survival rates in patients that achieve a pathological complete response (pCR). In patients with a tumor size less than 5 cm and no involvement of axillary lymph nodes, it may be advisable to consider a shorter chemotherapy regimen to evaluate the achievement of pCR percentages compared to longer regimens. Methods: We conducted an analysis of a cohort comprising 62 patients with triple-negative breast cancer in stages I and II that received 4 cycles of NAT with paclitaxel 80 mg/m2 weekly for 12 weeks plus carboplatin in AUC 5 doses every three weeks. Results: The median age within the cohort was 61 years (32-83) with an initial tumor size of 22 mm (10-82) and Ki67 expression of 54% (13-90). Ten patients (16%) presented histologically confirmed initial axillary involvement. The group attained a pCR rate of 56% while only 21% exhibited a minor response with a residual tumor exceeding 10 mm. Over a median follow-up period of 34 months, the recurrence rate was only 5%. The distribution of pathological response across the different clinical variables is delineated in the Table. Conclusions: The NAT regimen with carboplatin AUC 5 + weekly paclitaxel (80 mg/m2) for four cycles is safe for patients diagnosed with stage I and II, demonstrating a high pCR (56%) and a lower recurrence rate (5%). The pathological response observed across all clinical variable subgroups suggests that this regimen could be considered a potential standard for NAT in patients with stage I and II triple-negative breast cancer. [Table: see text]

A propensity-matched cohort study of neoadjuvant immunotherapy combined with chemotherapy versus neoadjuvant chemotherapy for early-stage triple-negative breast cancer.

e13134 Background: Preferred neoadjuvant treatment (NAT) regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. This study compared the efficacy, safety and biomarker exploration of camrelizumab combined with chemotherapy and chemotherapy as neoadjuvant treatment for early-stage TNBC. Methods: This study included 2 cohorts with different NAT regimens, matched (2:1) according to age, clinical T and N stage, and Ki-67 status. Patients in the immune combination chemotherapy (NIC) cohort were recruited from a phase II clinical trial (NCT04676997). NIC patients received intravenous camrelizumab at a dose of 200mg and simultaneous chemotherapy consisted of platinum-free drugs, or platinum containing drugs. Patients in the neoadjuvant chemotherapy (NAC) cohort regimen comprised 4 cycles of paclitaxel 175 mg/m2, and 4 cycles of epirubicin (90 mg/m2, d1, q2w) + cyclophosphamide (600 mg/m2, d1, q2w). The indicators of this study include pCR, breast pCR (bpCR), axillary lymph node dissection (ALND) rate, breast conserving surgery (BCS) rate and tumor immune microenvironment (TIME) analysis of gene expression profiling. Results: Of 252 eligible patients, 162 patients were identified in the analysis after propensity score matching (PSM). Compared with NAC alone, the addition of camrelizumab brought higher pCR rates (64.81% versus 37.04%, p<0.05), ALND rates (38.89% versus 12.96%, p<0.05) and comparable BCS rates (20.37% versus 15.74%, p<0.05). Gene expression analysis was performed on tumor tissue samples from 12 patients receiving NAC and 16 patients receiving NIC before and after NAT. The results showed that the TIME status of the NIC and NAC groups before treatment was basically the same. Moreover, we respectively compared the TIME status of patients with pCR and non_pCR in NIC and NAC before NAT. The results found that there were 9 significantly different signatures (p<0.05) between pCR and non_pCR patients in the NIC group, and 1 signature (p<0.05) in the NAC group, respectively. Notably, we found 8 signatures (B Cells, CD8 T Cells, TIS, IFN Gamma, Lymphoid, T Cell, APM, Immunoproteasome), that were scored significantly higher only in pCR patients in the NIC group compared with non-pCR patients, and 8 signatures could promote response to immunotherapy. The common difference signature between the two groups is Treg cells. Conclusions: In patients with early-stage TNBC, neoadjuvant treatment with camrelizumab plus chemotherapy significantly improved pCR with an acceptable safety profile. Differences in TIME may affect response to treatment regimens. Future validation in prospective randomized controlled trials with larger sample sizes is needed. Clinical trial information: NCT04676997 .

The Impact of Obesity on Success of Immediate Lymphatic Reconstruction for Prevention of Breast Cancer–Related Lymphedema

Background Breast cancer–related lymphedema (BRCL) is a potential sequela of high-risk breast cancer treatment. Preventive treatment with immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has emerged as the standard of care; however, there is relatively little known about factors that may contribute to procedural failure. Methods A retrospectively maintained, institutional review board–approved study followed patients who underwent ILR at the time of ALND at our tertiary care center between May 2018 and May 2023. Patients who presented for at least one follow-up visit in our multidisciplinary lymphedema clinic met the criteria for inclusion. Patients who developed lymphedema despite ILR and potential contributing factors were further explored. Results 349 patients underwent ILR at our institution between May 2018 and May 2023. 341 of these patients have presented for follow-up in our multidisciplinary lymphedema clinic. 32 (9.4%) patients developed lymphedema despite ILR. This cohort was significantly more likely to be obese (56% vs 35%, P = 0.04). Multivariate logistic regression demonstrates increased odds of procedural failure in patients with a body mass index (BMI) ≥30 kg/m2 (odds ratio 2.6 [1.2–5.5], P = 0.01). Conclusion These data comment upon our institutions outcomes following ILR. Patients who develop lymphedema despite ILR tend to have a higher BMI, with a significantly increased risk in patients with a BMI of 30 or greater. Consideration of these data is critical for preprocedural counseling and may support a BMI cutoff when considering candidacy for ILR going forward, as well as when optimizing failures for secondary lymphedema procedures.

Studying on correlation between Ki-67 index and histopathological and immunohistochemical characteristics in invasive breast carcinoma

Background: Breast cancer is the most common cancer and the leading cause of cancer death in women. Molecular subtyping of breast cancer is based on the expression of biomarkers such as ER, PR, HER2/neu and Ki-67. Among them, Ki-67 is a biomarker expressing the proliferation level of breast cancer cells, directly related to disease progression, treatment response and prognosis. Our study aims to evaluate the Ki-67 index and its relationship with histopathological and immunohistochemical characteristics in invasive breast carcinoma. Methods: A cross-sectional descriptive study in 101 paraffin-embedded specimens of patients with invasive breast carcinoma who underwent surgery at Hue University of Medicine and Pharmacy Hospital from October 2019 to June 2021. Results: Tumors with Ki-67 index ≥ 14% account for 65.3%. Breast cancer tumors with tumor size ≤ 2 cm occupy for 50.5%. Histological grade II accounts for 53.1%. The most common disease stage is stage II (40.6%). The rate of axillary lymph node metastasis is 48.5%; The ER(+) and PR(+) rates are 64.4% and 47.5%, respectively. Tumors with HER2(+) account for 32.7%. The Luminal B accounts for the highest proportion (39.4%). The Ki-67 index has a statistically significant relationship with disease stage, histological grade, axillary lymph node metastasis, ER, PR, HER2 and molecular subtypes. There is no relationship between Ki 67 and age, tumor size and histopathological type. Conclusion: Tumors with Ki-67 ≥ 14% account for a high proportion (65.3%). The Ki-67 index has a statistically significant relationship with histopathological and immunohistochemical features: stage of disease, histological grade, axillary lymph node metastasis, ER/PR hormone receptors, and other factors. HER2-positive endodermal growth and molecular subtypes. There is no significant relationship between Ki-67 and age, tumor size and histopathological type. Key words: breast carcinoma; Ki-67; histopathology; immunohistochemistry.

Relationship between receipt of combined axillary dissection and nodal irradiation and age.

11043 Background: Combined axillary lymph node dissection and regional nodal irradiation (ALND+RNI) is the greatest risk factor for breast cancer-related lymphedema (BCRL), a lifelong ailment that negatively impacts quality of life. As disability from BCRL may be particularly profound for adults <45 yo with longer life expectancy, we examined the association of age and other sociodemographics with receipt of ALND+RNI to further our understanding of patients at greatest risk for BCRL. Methods: The National Cancer Database (NCDB) was used to examine age-based differences in receipt of ALND+RNI in patients with stage I-III breast cancer treated from 2018-2020. Cohort characteristics were compared by age (<45 yo, 45-64 yo, and 65 yo). Multivariable regression examined the association between age and ALND+RNI adjusting for relevant factors. Sensitivity analyses explored associations between covariates and combined ALND+RNI by age group. Results: Of 155,010 patients, 5.4% were <45 yo, 47.2% were 45-64 yo, and 47.4% were 65 yo. Clinical and pathological node (cN, pN) positive disease, and receipt of ALND, RNI, and ALND+RNI were more common in patients <45 yo (Table). Age <45 yo was independently associated with ALND+RNI (<45 yo OR 1.40; 45-64 yo OR 1.26 vs 65, p<0.001). Residing in areas with a high proportion of high-school graduates (%HSG), Hispanic ethnicity but not race, and lower income were also associated with ALND+RNI in adjusted analyses (all p<0.05). Medicare (p=0.02 vs private insurance) was inversely associated with ALND+RNI. Among clinical factors, pN+ was the greatest risk factor for receipt of ALND+RNI (all p<0.001 vs pN0). Higher cT, cN1 and cN2 categories, lobular tumors, mastectomy, not receiving endocrine therapy, and having chemotherapy were also associated with ALND+ RNI (all p<0.05). Sensitivity analyses showed that while sociodemographics influenced receipt of ALND+RNI for women 45 yos, only clinical factors were significant for ALND+RNI for <45 yo. Among 45-64 yo, high %HSG (p<0.001) and low household incomes (p<0.01) were associated with ALND+RNI. In the 65 yo cohort, high %HSG (p=0.028), and Asian race (p=0.011) were more likely to receive ALND+RNI while Medicare patients were less likely to have ALND+RNI (p=0.012). Conclusions: Our findings suggests that clinical factors predominate in axillary treatment decisions for younger patients; while sociodemographic factors are more prominent for those 45 yo. Given their higher odds of receiving ALND+RNI, BCRL screening may be especially important in patients <45 yo. Further studies are needed to understand the interplay between age and sociodemographics on receipt of ALND+RNI. [Table: see text]

A prospective, open-label, single-arm phase II clinical study of inetetamab in combination with pyrotinib and albumin-bound paclitaxel for the neoadjuvant treatment of patients with HER2+ early and locally advanced breast cancer.

e12635 Background: Chemotherapy combined with dual anti-HER2 target therapy has become the standard neoadjuvant therapy regimen for HER2+ breast cancer. Patients achieving pCR have a relatively better prognosis. Inetetamab (Septin) is an innovative HER2 monoclonal antibody drug developed in China. It has been proven to delay the progression of HER2+ metastatic breast cancer patients and bring survival benefits. The purpose of this study was to explore the efficacy and safety of Inetetamab, Pyrotinib and Albumin-bound Paclitaxel in the neoadjuvant treatment of HER2+ breast cancer. Methods: This phase II trial included patients with HER2+ early or locally advanced breast cancer whose tumor size was>20mm or confirmed axillary lymph node metastasis. Patients receive Inetetamab initial dose of 8 mg/kg over 90 minutes IV infusion, followed 6 mg/kg over 30 to 90 minutes IV infusion q3w, Pyrotinib 400 mg orally every day and Albumin-bound Paclitaxel 125mg/m2, IV, D1/8/15, q3w. Patients receive above treatment every 3 weeks for a total of 4 cycles, followed by surgery. After surgery, EC (90mg/m2 of Epirubicin Hydrochloride, 600mg/m2 of Cyclophosphamide, q21 days, 4 cycles) was administered, followed by maintenance treatment with trastuzumab combined with pertuzumab for 1 year. And provide radiotherapy and endocrine therapy to the patient according to the specific situation. The primary endpoint was pathological complete response (pCR). Results: Until February 4, 2024, 18 patients were enrolled, of which 15 had completed surgical treatment. The median age of enrolled patients was 49 years (35-60 years). 66.7% (10 cases) of patients achieved RCB grade 0 (pCR), 26.7% (4 cases) achieved RCB grade I, 6.7% (1 case) achieved RCB grade II. Of the 15 patients, 73.3% (11 cases) were HR+/HER2+, with 72.7% (8 cases) achieved pCR. Among the 4 HR-/HER2+ patients, 50% (2 case) achieved pCR. HR+/HER2+ patients were more likely to achieve pCR than HR-/HER2+ patients. No severe (grade 3/4) toxicity was observed in any patients. Conclusions: Our current data show that the pCR rate in HER2+ breast cancer patients reaches 66.7%, and even 72.7% in HR+ patients. In the previous Neosphere and PEONY studies of the H+P dual target regimen, the pCR of HR+/HER2+patients increased by only 6% and 8.3%, while in the NeoALTTO and PHEDRA studies of the H+L or H+Py regimen, the pCR increased by 18.9% and 17.7%, indicating that the combination of large and small molecules with dual target neoadjuvant therapy for HR+/HER2+ breast cancer was significantly better than that of the monoclonal antibody dual target therapy. Therefore, Inetetamab, Pyrotinib and albumin-bound paclitaxel is a potential effective new adjuvant treatment for HER2+ breast cancer, especially for HR+ patients. Clinical trial information: NCT054444998 .

Axillary lymph nodes pCR (apCR) versus breast pCR (bpCR): A meta-analysis involving 10,723 patients.

e12630 Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) may improve the long-term survival of patients with breast cancer, as scored by disease-free survival (DFS) and overall survival (OS). Axillary lymph node pCR (apCR) is an important prognostic factor and may influence surgical de-escalation strategies; however, there is insufficient evidence to confirm that apCR produces a better prognosis than breast pCR (bpCR). The study aimed to perform a meta-analysis to assess the effect of apCR on survival compared with bpCR. Methods: We searched Cochrane Library, Web of Science, PubMed, Embase, and Clinical Trials.gov for breast cancer clinical trials with NAC. For included studies, we extracted the following data for analysis: study details, characteristics of participants, and survival data. Outcome data were reported as hazard ratios (HRs) and 95% confidence interval (CI) to measure the association between pCR and DFS, and OS. An I² test and subgroup analyses were performed to assess statistical heterogeneity in the included studies. Egger’s test and Begg’s funnel plot were used to determine potential publication bias. Results: We obtained data from 12 studies with 10,723 patients. Those patients with apCR had significantly better DFS than those with bpCR (HR=0.67, 95% CI, 0.60-0.76, P<0.00001), and no significant heterogeneity was observed between studies (I2=0%). As for OS, the HR significantly supported apCR (HR=0.72, 95% CI, 0.60-0.86, P=0.0002). There was no significant heterogeneity between studies (I2=35%). Subgroup analyses of each variable did not alter the results. Egger's test and Begg’s funnel plots indicated no significant publication bias in this analysis. Conclusions: This meta-analysis demonstrated that apCR is strongly associated with better DFS and OS than bpCR. This finding suggests that apCR has the potential to be an early surrogate endpoint for long-term prognosis.

Trastuzumab biosimilars interchangeability: Preliminary real-world data in neoadjuvant breast cancer setting.

e23305 Background: Interchangeability (IC) among biosimilar compounds is still an issue not completely addressed, due to concerns on adverse events, immunogenicity, and efficacy. Many regulatory agencies around the world have adopted IC aside of appropriate clinical trials evaluation. Brazil’s Public Health System (SUS) has centrally provided trastuzumab (T) for breast cancer (BC) and firstly adopted biosimilars in 2020, after their regulatory approval 2 years before. After T biossimilar adoption there was an improvement of access for its all clinical indications, however different compounds had been offered to patients (pts) along their treatment. The aim of this study is evaluating the impact of these exchanges of types of T on patient-based registry. Methods: We reviewed all pharma and clinical data between 2020 and 2022 from all pts, stage III, Her2-Positive, who received neoadjuvant treatment based on chemotherapy plus trastuzumab in a Comprehensive Cancer Center in Southern Brazil. The main objective is measuring the rates of changes among T biosimilar compounds, and its impact in pathological response (pCR), toxicity and treatment-failure rates. Chi-square, Fisher’s Exact, t-test, or Mann-Whitney testing, as appropriate, was used to compare events between groups. Results: Along the studied period, SUS had offered 3 T biosimilars: ABP 980 (Amgen), CT-P6 (Celltrion), SB3 (Samsung), plus reference trastuzumab (Roche). The standard regimen was ACq21 4cycles followed by Taxane (Docetaxel q21 or weekly Paclitaxel) plus T 4cycles. 146 pts were eligible to analysis. 83 pts received only one type of T compound (non-interchangeability group – NICG), 63 pts received at least 2 different T compounds along the treatment (Interchangeability Group – ICG). Both groups were comparable in terms of clinical features (age, ER/PR status, menopausal status, PS, tumor size, and staging of axillary lymph nodes). Rate of IC along the time was 11%, 53% and 33% in 2020, 2021 and 2022, respectively. pCR was 32,5% in NICG versus 33,3% in ICG (p:NS). In total, 3pts had their treatments interrupted due to toxicity (1pt cardiac, 2pts hematologic). Conclusions: Although IC among biosimilars compound had been globally accepted, it was not clinically fully tested. Brazilian Ministry of Health, as the only provider, has a policy based on lowest cost for trastuzumab compound, causing constant changes along pts treatments. Furthermore, it is expected that Brazil has the potential to evaluate the IC in thousands of pts prospectively next years. Hereby, we could demonstrate preliminary based on retrospective data that exchange among different biosimilar compounds did not interfere significantly on pCR, nor raised any new safety or clinical concerns.

Treatment outcomes and survival of patients with breast cancer aged 75 and older: A comparative study using propensity score-adjusted analysis.

e13763 Background: With an aging society, the incidence of breast cancer among elderly patients is expected to rise. We aimed to explore treatment outcomes in breast cancer patients aged 75 and older at our institution. The lack of consensus on whether adjuvant therapy for elderly breast cancer patients should mimic that for younger patients prompted our investigation. Methods: We conducted a comparative study using data from 1553 breast cancer surgery cases (stage 0-3) treated between April 2007 and August 2021. Patients were divided into two groups: those aged 75 and older (n=184) and those aged 74 and younger (n=1369). Variables investigated included mean age, tumor size, stage, and subtype; surgical procedures and adjuvant therapies; overall survival (OS); and OS in the 75 and older group, considering the presence or absence of hormone therapy, and propensity score-adjusted OS. Results: Comparing the group aged 74 and younger with the group aged 75 and older revealed: Mean age: (55.5 years vs. 79.6 years), tumor size: (2.4 cm vs. 2.3 cm), stage (0/1/2/3) (%): (7.3/43.1/44.1/4/6 vs. 7.6/43.4/43.4/5.7), subtype (Luminal A/Luminal B/TN/HER2) (%): (60.0/16.7/11.3/7.9 vs. 63.5/10.7/15.7/5.7). Except for age, no significant differences were observed. Mastectomy (%): 45.9 vs. 50.8, axillary lymph node dissection (%): 33 vs. 22.3, adjuvant therapy (%): 93.2 vs. 65.7, adjuvant hormone therapy (%): 90 vs. 68, adjuvant chemotherapy (%): 68 vs. 14. The group aged 75 and older received significantly less adjuvant hormone therapy and chemotherapy. Kaplan-Meier 10-year OS rates: 90.3% vs. 77.5%, showing a trend toward lower survival in the group aged 75 and older, albeit not statistically significant. No significant differences were found in overall survival rates by subtype. In the group aged 75 and older, hormone therapy was omitted in 44.6% and administered in 55.4%, resulting in a significant difference in 10-year OS rates (63.5% vs. 84.7%). Following propensity score adjustment for age, stage, and subtype, the hormone therapy-free group exhibited a higher 10-year OS rate of 100%, in contrast to 84.7% in the hormone therapy group. Conclusions: Breast cancer cases in patients aged 75 and older show similar biological characteristics to those aged 74 and younger. The absence of adjuvant therapy does not impact OS, even though elderly patients aged 75 and older are less likely to receive adjuvant hormone therapy and chemotherapy.

Defining musical toxicity after breast cancer treatment: A classification tree analysis.

12048 Background: Playing music has been an important part of human culture for millennia. Today more than half of American households have at least one person who plays music, and in the UK 43% of adults play an instrument. Despite the overlap between musicians and people diagnosed with cancer, the effect of cancer treatment on musicianship has not been well-studied. We previously reported that 26% of a musician breast cancer survivor cohort reported difficulty with musicianship after treatment, and here we conduct further analysis to identify treatment and disease factors associated with this difficulty, termed acute musical toxicity (AMT). Methods: The Musical Toxicity Questionnaire was distributed to participants who had previously enrolled in the Mayo Clinic Breast Cancer Registry. PROMIS (Patient-Reported Outcomes Measurement Information System) scores were available through the Registry and treatment details were collected retrospectively. Due to the inter-dependency and high correlation between treatment and disease-related variables, a classification tree analysis (CTA) was performed to identify the combination of variables that most accurately classified patients by AMT. Sixteen variables were analyzed by the algorithm. Logistic regression was utilized for examining associations between AMT and continuous variables. Results: Of the 4075 surveys distributed, 1871 were returned and 535 respondents identified as musicians. Median time from diagnosis was 5.2 years, respondents were mostly stage I or II (71%), and 32% were node positive (N+). Over a quarter (26% or 144 respondents) reported AMT. In the final CTA model, being N+ was strongly associated with AMT (42% of those N+ had AMT, 20% of those not N+ had AMT). For respondents who were N+, those who received endocrine therapy were more likely to have AMT than those who did not (46% vs 21% respectively). Subsequent leaves identified not undergoing axillary lymph node dissection (ALND) and receiving chemotherapy as associated with AMT. For respondents who did not receive chemotherapy, breast reconstruction was associated with AMT (60% vs 19%). Variables such as mastectomy, radiation volume, specific chemotherapies, and stage of disease were not selected by the algorithm. The odds of having AMT decreased by 9.7% and 17% with each additional point in the composite mental health (p=0.003) and physical health (p<0.001) PROMIS scores, respectively. The odds of having AMT increased by 3.5% with each lymph node removed (p=0.001). Conclusions: The final model suggests that the group with the largest proportion of AMT was N+, received endocrine therapy, did not have ALND, and received chemotherapy. Both physical and mental health PROMIS scores were associated with AMT, although the directionality of this relationship requires more study. Care teams should counsel patients on potential musical toxicity and engage in shared decision making with musical patients.

Racial and ethnic disparities in hospital outcomes following hospitalizations for mastectomy for breast cancer.

e13691 Background: Racial and ethnic disparities in breast cancer (BC) treatment and survival have been well documented. White (W) and Asian (A) women are more likely to have localized BC (BC) than Black (B) or Hispanic (H) women. Furthermore, the incidence of triple negative BC is higher in B women who also have the highest death rates from BC. In this study, we aimed to identify an association between race/ethnicity and outcomes following hospitalization for mastectomy using a large national database. Methods: This study isa retrospective analysis of the National Inpatient Sample database, the largest all-payer inpatient database in the United States, of hospitalizations between 2016-2019. Patients (pts) ≥18 years of age, admitted for mastectomy for BC were included and stratified by race/ethnicity. The outcomes of the study were in-hospital mortality rate, prolonged hospital length of stay, surgical site infection, bleeding complication, cardiac complication, respiratory complication, acute kidney injury, urinary tract infection, and wound dehiscence. Hospitalizations and outcomes were identified using ICD-10 diagnosis and procedure codes. Logistic regression analysis was done to identify an association between race and outcomes. Results: A total of 302,208 pts who were hospitalized for mastectomy were included. Of these 218,092 (72.2%) pts were W, 36,242 (12.0%) were B, 25,130 (8.3%) were Hispanics, and 22,744 (7.5%) were of another race. Among B pts, adverse outcomes were significantly higher (p<0.001), including in-hospital mortality rate (0.2%), prolonged hospital length of stay (64.1%), surgical site infection (0.8%), bleeding complication (4.2%), cardiac complication (0.8%), respiratory complication (0.3%), and acute kidney injury (1.4%). After adjusting for various factors including age, insurance, hospital region, hypertension, diabetes, obesity, peripheral vascular disease, alcohol use, Elixhauser comorbidity index, whether pts underwent axillary lymph node dissection and others, logistic regression was performed. This analysis identified that B pts had significantly higher odds for mortality (adjusted odds ratio [aOR], 2.99, 95% CI: 1.62-5.73), prolonged hospital length of stay (aOR, 1.32, 95% CI: 1.18-1.49), and bleeding complication (aOR, 1.28, 95% CI: 1.13-1.48). Conclusions: Results of our study show that adverse hospital outcomes following mastectomy for BC were significantly higher among Black patients. These outcomes remained significant after adjusting for clinical covariates, raising the possibility of other contributing factors to these differences in outcomes. Study limitations include the lack of information on stage at diagnosis, receptor status, and that Hispanics were categorized under race. Further studies are needed to develop effective interventions to reduce these disparities.

Role of NEDD9 expression in non-metastatic HER2-positive breast cancer.

e12645 Background: Neural Precursor Cell Expressed Developmentally Downregulated Protein 9 (NEDD9) is a member of the associated substrate family. Our previous studies demonstrated the role of NEDD9 overexpression in early tumorigenesis in HER2-positive (HER2+) breast cancer in vivo. Tissue microarray-based analysis showed a strong correlation between NEDD9 mRNA and relapse-free survival (RFS) and pathologic complete response (pCR) rate in HER2+ breast cancers. In this study, NEDD9 expression in non-metastatic HER2+ breast cancer was evaluated by tissue microarray. Methods: A total of 64 patients with non-metastatic HER2+ cancer of the breast who had received neoadjuvant chemotherapy and had sufficient pathology specimens were included in the study. NEDD9 was stained by tissue microarray, and the expression was subclassified as low, intermediate, and high based on the NEDD9 expression score. The correlations of NEDD9 expression with the clinical/biological characteristics, treatment, and treatment response were analyzed by Fisher Exact test. Results: A total of 64 patients were included in the study, with a medium follow-up duration of 4.6 years. The median age was 54, 1 patient was male, 79.3% of patients had stage 2 disease, 1 patient had inflammatory breast cancer, and 37.5% of patients had ER/PR negative disease. The most common neoadjuvant chemotherapy regimen was TCHP (82.5%), 44.4% of patients underwent lumpectomy, and 67.7% of patients underwent axillary lymph node dissection (ALND). 54% of patients achieved complete pathologic response (pCR), all patients received adjuvant anti-HER2 treatment, 85.7% received adjuvant radiotherapy, and 74.6% received adjuvant endocrine therapy. The NEDD9 expression distribution for low, intermediate, and high were 37.5%, 50.0%, and 12.5%, respectively. NEDD9-high patients had higher tumor stage and grade than NEDD9-low/ intermediate patients (p = 0.004, p= 0.041). More NEDD9-high patients underwent ALND compared to NEDD9- low/intermediate patients (p = 0.09). There is no statistically significant difference in pCR rate between NEDD9 expression groups, although numerically more NEDD9-high patients achieved pCR (75%, 56.2%, and 43.5% in NEDD9-high, intermediate, and low patients). Conclusions: In non-metastatic HER2+ breast cancer, NEDD9 expression is associated with more advanced tumor grade and stage. There is no statistically significant difference in pCR rate between groups, although more patients achieved pCR with a higher level of NEDD9 expression. The sample size limits our study. Additional study is needed to evaluate the correlation between NEDD9 expression and pCR rate following neoadjuvant chemotherapy in HER2+ breast cancer.

Value of Contrast-Enhanced Ultrasound Combined with Immune-Inflammatory Markers in Predicting Axillary Lymph Node Metastasis of Breast Cancer

ObjectiveTo evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with immune-inflammatory markers in predicting axillary lymph node metastasis (ALNM) in breast cancer patients. MethodsFrom January 2020 to June 2023, the clinicopathological data and ultrasound features of 401 breast cancer patients who underwent biopsy or surgery were recorded. Patients were randomly divided into a training set (321 patients) and a validation set (80 patients). The risk factors for ALNM were determined using univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis, and prediction models were constructed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess their diagnostic performance. ResultsLogistic regression analysis demonstrated that systemic immunoinflammatory index (SII), CA125, Ki67, pathological type, lesion size, enhancement pattern and Breast Imaging Reporting and Data System (BI-RADS) category were significant risk factors for ALNM. Three different models were constructed, and the combined model yielded an AUC of 0.903, which was superior to the clinical model (AUC = 0.790) and ultrasound model (AUC = 0.781). A nomogram was constructed based on the combined model, calibration curve and DCA demonstrated its satisfactory performance in predicting ALNM. ConclusionThe nomogram combining ultrasound features and immune-inflammatory markers could serve as a valuable instrument for predicting ALNM in breast cancer patients. Data availability statementThe original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Clinicopathological features and prognosis for pregnancy-associated breast cancer: A matched case-control study.

e12573 Background: Pregnancy-Associated Breast Cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 1 year postpartum. Studies indicate that PABC tends to have poorer prognostic characteristics and often worse outcomes compared to non-PABC. The primary goal of this study is to examine disease characteristics associated with PABC versus non-PABC in the United Arab Emirates (UAE), where breast cancer is characterized by a younger age and more advanced stage compared to North America and Europe. Additionally, the UAE has a younger mean age for first-time mothers and a similar age for all mothers compared to North America and Europe. Methods: Patients with PABC were selected from BC cases of women ≤40 years treated at Tawam Hospital, the largest tertiary cancer center in the UAE between January 2003 – December 2020. Each PABC patient was matched to two non-PABC patients (controls) according to cancer stage, age, and year of diagnosis. The Fisher's exact and Kruskal-Wallis tests were used to compare both study groups. Results: 66 women with PABC were identified, with a median age at diagnosis of 33.0 (interquartile range [IQR]: 30.0-37.0) years. Most presented with stage II (45.5%) or stage III (39.4%) disease and underwent mastectomy and axillary lymph node dissection. Invasive ductal carcinoma was the most frequent histological type in both groups (86.4% for PABC and 85.6% for non-PABC). PABC was associated with higher grade 3 disease compared with non- PABC (53% vs 51.5% p= 0.009). More women with PABC received neoadjuvant chemotherapy (NACT) and radiation therapy (RT) compared with non-PABC (48.5% vs 3%, p <0.001 and 80.3% vs 65.9%, p= 0.046, respectively). There were no statistically significant differences with regards to tumor size, nodal involvement, underlying histologic subtype, ER/PR expression or HER-2 status, rates of breast-conserving surgery and adjuvant chemotherapy receipt between the two groups. The median progression-free survival (PFS) was 3.2 years (IQR: 1.9-7.1) in PABC and 3.4 years (IQR: 1.2-6.2) in non-PABC group (P=0.306). The median overall survival (OS) was 4.5 years in the PABC (IQR: 2.4-7.9) versus 4.5 years (IQR: 1.9-7.9) in the non-PABC group (P = 0.786). Conclusions: PABC in women ≤40 years appears to be associated with grade III tumors and NACT and RT receipt compared to non-PABC. However, there were no significant difference in PSF and OS between PABC and non-PABC. Further analysis is underway to evaluate the prognostic factors and their effect on survival.

AI-based quantification of TILs using hematoxylin and eosin and immunohistochemistry-stained slides in triple-negative breast cancer.

e13608 Background: The importance of accurately understanding the status of tumor-infiltrating lymphocytes (TILs) in the preoperative chemotherapy context, for triple-negative breast cancer is underscored, highlighting the dual role of TILs in gauging treatment efficacy and prognostication. However, the difficulty in quantitatively and objectively assessing TILs in clinical practice is acknowledged, noting the barrier to its adoption as a standard diagnostic end-point. This study proposes a novel AI-based method to overcome these challenges, by quantitatively assessing TILs using hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, and exploring their prognostic relationship. Methods: In this study, 68 cases of breast cancer with axillary lymph node metastasis at the time of resection, were selected from a total of 3,902 resections conducted between 2002 and 2016. To quantitatively assess TILs, we developed a quantitative assessment method, integrating an AI-based epithelial detection model and non-rigid image registration techniques to align H&E and IHC-stained images for precise measurement of immune markers (CD3, CD8, FOXP3, PD-L1) within the tumor stroma. Using an AI-based model trained on 12,273 annotated epithelial images, the stroma, excluding the epithelium, was identified. The tumor bed was also defined by a pathologist. Finally, we assessed the prognostic significance of the TILs for disease-free survival (DFS) through ROC analysis and log-rank tests. Results: Optimal thresholds for CD3 (0.152 mm²), CD8 (4.8 mm²), FOXP3 (0.25 mm²), and PD-L1 (0.115 mm²) were identified, with corresponding AUCs of 0.678, 0.625, 0.746, and 0.659. Patients with cell counts or areas above these thresholds demonstrated improved DFS (P<0.05 for all markers). Conclusions: These findings suggest that the quantification of immune cells within the tumor bed provides reliable prognostic indicators for recurrence. The AI-based TILs quantification offers a significant advancement in the prognostic assessment of triple-negative breast cancer. In addition, it improves the objectivity and clinical utility of pathological evaluations. This precise measurement of TILs could be transformative in patient prognostication and the formulation of treatment plans.

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

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

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

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