Node-positive Breast Cancer Research Articles

Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Current axillary management of patients with early breast cancer and low-volume nodal disease undergoing primary surgery: results of a United Kingdom national practice survey

PurposeUK NICE guidelines recommend axillary node clearance (ANC) should be performed in all patients with biopsy-proven node-positive breast cancer having primary surgery. There is, however, increasing evidence such extensive surgery may not always be necessary. Targeted axillary dissection (TAD) may be an effective alternative in patients with low-volume nodal disease who are clinically node negative (cN0) but have abnormal nodes detected radiologically. This survey aimed to explore current management of this group to inform feasibility of a future trial.MethodsAn online survey was developed to explore current UK management of patients with low-volume axillary disease and attitudes to a future trial. The survey was distributed via breast surgery professional associations and social media from September to November 2022. One survey was completed per unit and simple descriptive statistics used to summarise the results.Results51 UK breast units completed the survey of whom 78.5% (n = 40) reported performing ANC for all patients with biopsy-proven axillary nodal disease having primary surgery. Only 15.7% of units currently performed TAD either routinely (n = 6, 11.8%) or selectively (n = 2, 3.9%). There was significant uncertainty (83.7%, n = 36/43) about the optimal surgical management of these patients. Two-thirds (n = 27/42) of units felt an RCT comparing TAD and ANC would be feasible.ConclusionsANC remains standard of care for patients with low-volume node-positive breast cancer having primary surgery in the UK, but considerable uncertainty exists regarding optimal management of this group. This survey suggests an RCT comparing the outcomes of TAD and ANC may be feasible.

Residual Axillary Metastases in Node-Positive Breast Cancer Patients After Neoadjuvant Treatment: A Register-Based Study

BackgroundLymph node (LN) metastasis after neoadjuvant chemotherapy (NACT) generally warrants axillary lymph node dissection, which opposes guidelines of upfront surgery in many cases. We investigated the risk of having additional metastases in the axilla when the LNs removed by targeted axillary dissection (TAD) harbored metastases after NACT. We aimed to identify subgroups suitable for de-escalated axillary treatment.MethodsThis register-based study used data from the Danish Breast Cancer Cooperative Group database. Data were analyzed with logistic regression models. The primary outcome was the metastatic burden in non-TAD LNs in patients with positive TAD LNs after NACT.ResultsAmong 383 patients, < 66.6% positive TAD LNs (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17–0.62), only isolated tumor cells (ITCs) [OR 0.11, 95% CI < 0.01–0.82], and breast pathological complete response (pCR) [OR 0.07, 95% CI < 0.01–0.56] were associated with a low risk of having more than three positive non-TAD LNs. In 315 patients with fewer than three positive non-TAD LNs, the proportion of positive TAD LNs (OR 0.45, 95% CI 0.27–0.76 for 33.3–66.6% vs. > 66.6%), size of the TAD LN metastasis (OR 0.14, 95% CI 0.04–0.54 for ITC vs. macrometastasis), tumor size at diagnosis (OR 0.30, 95% CI 0.15–0.64 for 20–49 mm vs. ≥ 50 mm) and breast pCR (OR 0.38, 95% CI 0.15–0.96) were associated with residual LN metastases in the axilla.ConclusionsBreast pCR or ITC only in TAD LNs can, with reasonable certainty, preclude more than three positive non-TAD LNs. Additionally, patients with only ITCs in the TAD LN had a low risk of having any non-TAD LN metastases after NACT. De-escalated axillary treatment may be considered in both subgroups.

Abstract PO1-03-02: Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial

Abstract Background: The long-term results of the Italian randomized phase III GIM2 study showed that, in women with node-positive breast cancer (BC), dose-dense (DD) chemotherapy significantly improved both disease-free survival (DFS) and overall survival (OS) compared with standard-interval (SI) chemotherapy. Obesity has been identified as an independent poor prognostic factor in patients with BC, with a potential negative impact on the efficacy and toxicity of systemic therapies. Nevertheless, the specific influence of body mass index (BMI) on the efficacy of different adjuvant chemotherapy schedules (DD or SI) remains a subject of debate. This analysis aimed to investigate this hypothesis in patients enrolled in the GIM2 trial. Methods: GIM2 was a randomized multicentric phase III trial that compared different chemotherapy schedule (DD vs SI) and regimen (FEC-P vs EC-P) in 2091 node-positive early breast cancer patients. BMI (kg/m2) was categorized as follows: &amp;lt; 18.5 (underweight), 18.5 to &amp;lt; 25 (lean), 25 to &amp;lt; 30 (overweight), and ≥ 30 (obese). The primary endpoint was to assess association between BMI and DFS and OS. Survival estimates were compared using the Kaplan-Meier method and log-rank test. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: A total of 1925 patients were included in the present analysis, of whom 31.6% (n=632) were overweight and 19.3% (n=386) obese. Median age was 52 years. Overweight-obesity condition was significantly associated with postmenopausal status, greater representation of T2-T4 tumors with N &amp;gt; 2 in both patients in the DD and SI arm. After a median follow-up of 15.0 years (IQR 8.4-16.3), compared to patients with normal BMI, those who were overweight or obese at diagnosis had a higher risk of experiencing a DFS event (Hazard Ratio [HR] 1.11 95% CI 0.94-1.31 and HR 1.37 95%CI 1.14-1.65, respectively, p=0.003) and OS event (HR 1.11 95% CI 0.89-1.38 and HR 1.59 95%CI 1.26-2.01, respectively, p=0.0003). No significant interaction was found between BMI and treatment schedule in terms of DFS (p for interaction=0.56) nor OS (p for interaction=0.19). At the multivariate analysis, in the DD arm, adjusted HR (aHR) for DFS and for OS were 1.01 (95% CI 0.75- 1.35) and 1.04 (95% CI 0.72-1.52) for obese vs. normal BMI groups, and 0.88 (95% CI 0.68- 1.15) and 0.77 (95%CI 0.54-1.10) for overweight vs. normal BMI groups, respectively. In the SI arm, aHRs for DFS and OS were 1.24 (95% CI 0.94- 1.63) and 1.35 (95%CI 0.96- 1.90) for obese vs. normal BMI groups, and 1.04 (95%CI 0.82- 1.33) and 1.01 (95% CI 0.74-1.40) for overweight vs. normal BMI groups, respectively. Similar results were observed when considering hormone receptor-positive and negative BC separately. Conclusion: In the GIM2 trial, BMI was prognostic but not predictive of different benefit to adjuvant chemotherapy. In high-risk patients, DD schedule should be considered the preferred schedule irrespective of BMI. Citation Format: Francesca Poggio, Eva Blondeaux, Marco Tagliamento, Marta Perachino, Simone Nardin, Benedetta Conte, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Ylenia Urracci, Maria Grazia Alicicco, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Luca Boni, Matteo Lambertini, Lucia Del Mastro. Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial [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 PO1-03-02.

Abstract PO2-23-06: Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer

Abstract Background The probability of axillary lymph node converting from positive to negative after neoadjuvant systemic therapy (NST) for breast cancer patients is approximately 40%. A variety of axillary lymph node biopsy surgeries based on sentinel lymph node biopsy (SLNB) can help to omit axillary lymph node dissection (ALND). The common disadvantages, however, are mainly the restrictions, such as the need for strict regulation of the use of radiotracers, the high number of retrieved lymph nodes required, and the need to purchase ancillary equipment. The more restrictions there are, the more they limit the spread and availability of the technique and, more importantly, reduce the number of patients who will benefit. In fact, for patients with metastatic lymph nodes, the sentinel lymph nodes must be included in the lymph nodes that have metastasized. If these metastatic lymph nodes can be accurately marked and precisely retrieved after NST, it is possible to assess whether the axillary lymph nodes are converted from positive to negative without the need for SLNB. Materials and methods Breast cancer patients with pathologically confirmed axillary lymph node metastases who were receiving NST were recruited for this study. Before NST, carbon nanoparticles suspension injections were injected into the cortex of the pathologically confirmed metastatic lymph node to stain the region where the metastatic lymph node was located. The lymph nodes in the stained region were retrieved by stained region lymph node biopsy (SrLNB) during the axillary surgery, followed by ALND, without the use of SLNB. Finally, the identification rate and false-negative rate (FNR) of SrLNB were statistically analyzed according to pathology data. Results A total of 159 patients were successfully enrolled in this study between September 24, 2020 and December 2, 2022, with an axillary pCR rate of 40.9% (65/159). The identification rate of SrLNB was 100% (159/159), with an overall FNR of 5.3% (5/94). Subgroup analysis revealed that in the subgroups of 1, 2, 3 and ≥4 SrLN, the FNR was 0%, 0%, 0% and 8.9% (5/56), respectively, whereas in the cN1, cN2 and cN3 subgroups the FNR was 7.7% (3/39), 2.6% (1/38) and 5.9% (1/17), respectively. The FNR indexes were within the safety threshold of 10% in all subgroups. Conclusion SrLNB has a high identification rate and a low FNR and is useful for screening patients with positive to negative axillary lymph nodes for omitting ALND. srLNB requires only the use of an affordable and radiation-free carbon nanoparticles suspension injection for marking, making the whole technique simpler and easier to disseminate. The data from this study also suggest that SLNB may not be mandatory for axillary biopsy in patients with positive axillary lymph nodes undergoing NST. Table 1. General characteristics of enrolled patients. Table 2. Analysis of factors affecting axillary pCR rates. Table 3. Analysis for the FNR of SrLNB. Citation Format: Jue Wang, Rui Chen, Cuiying Li, Hailing Zha, Qiannan Zhu, Lifeng Huang, Xiaoming Zha. Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph 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 PO2-23-06.

Abstract PO3-22-09: Implementation of nanoparticle-assisted axillary staging: reduced axillary intervention for patients with node-positive breast cancer following neoadjuvant therapy

Abstract Background: Nanoparticle-assisted axillary staging (NAAS), which combines carbon nanoparticles with standard dual-tracer (radioisotope and blue dye) sentinel lymph node biopsy (SLNB), has shown excellent results in patients undergoing neoadjuvant therapy (NAC) for pre-NAC node-positive breast cancer. This pilot study aimed to explore the possible expansion of indications (pre-NAC cN2, and cN3 stages; ycN+ stage) for NAAS, which was the first attempt till now for patients undergoing NAC, and to select specific post-NAC individuals who might be exempt from axillary lymph node dissection (ALND), especially those with relatively low tumor burdens, such as ITCs and micrometastases. Method: The medical records of all consecutive patients with breast cancer were prospectively collected from the Breast Center, West China Hospital. Patients with invasive, pre-NAC node-positive breast cancer who underwent NAAS followed by ALND between April 2021 and February 2023 were included. The detection rate (DR), average number of sentinel or NAAS nodes, false negative rate (FNR), negative predictive value (NPV), and NAAS accuracy were assessed. Subgroup analyses according to different pre- and post-NAC cN stages, especially the pre-NAC cN2-3 stages and the post-NAC cN+ stages, which were not the focus of previous studies, were conducted using crosstabs. To screen possible patients who might exempt ALND, we focus on relationships between the status of axillary lymph nodes and the number or tumor burden of NAAS nodes. Results: A total of 241 eligible patients were included in the study. There were 153 (63.49%), 40 (16.60%), and 48 (19.92%) patients in pre-NAC cN1, cN2, and cN3 stages, respectively. The post-NAC stages of patients were not restricted, 38.17% (92/241) of them converted to ycN0 stages, while 61.83% (149/241) were still in ycN+ stages. A total of 232 (96.27%) eligible patients successfully underwent NAAS; the DR, NPV, accuracy, and FNR of NAAS were 96.27%, 95.97%, 97.84%, and 4.42%, respectively. Additionally, NAAS showed accuracies of 97.30% and 93.02% and FNRs of 7.14% and 9.09% in patients with pre-NAC cN2 and cN3 breast cancers, respectively. There was no statistical difference among the FNRs of NAAS in the pre-NAC cN1, cN2, and cN3 stages (p=0.134). Moreover, NAAS yielded FNRs of 0.00% in the ycN0 population and 6.02% in the ycN+ population, respectively (p=0.323). Accuracies reached 100.00% and 96.48% in ycN0 and ycN+ patients, respectively (p=0.159). Notably, patients with one NAAS node with ITC or micrometastasis in the entire population showed no further positive disease at ALND. Conclusion: NAAS showed excellent and stable performance with a low FNR and high accuracy, indicating valuable application prospects in patients with breast cancer who received NAC. Patients with pre-NAC cN2-3 stages also have a chance to undergo NAAS, and the application of NAAS appears to be feasible regardless of the ycN stage. Especially for ycN0 population, there is no chance for NAAS to miss positive axillary lymph nodes. In addition, patients who had one NAAS node with ITC or micrometastasis might avoid ALND. Diagnostic performance of nanoparticle-assisted axillary staging in pre-neoadjuvant chemotherapy cN1, cN2 and cN3 patients Diagnostic performance of nanoparticle-assisted axillary staging in ycN0 and ycN+ patients Additional axillary disease at axillary lymph node dissection in patients with positive NAAS nodes after neoadjuvant chemotherapy XX- XX XX- XX XX- XX Citation Format: Ruixian Chen, Tao He, Jiqiao Yang, Shan Lu, Yunhao Wu, Chihua Wu, Ruoning Yang, Weijing Liu, Ya Huang, Xiangyue Meng, Xin Zhao, Qintong Li, Xin Sun, Jing Jing, Jie Chen. Implementation of nanoparticle-assisted axillary staging: reduced axillary intervention for patients with node-positive breast cancer following neoadjuvant therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-09.

Abstract PO4-05-12: High expression of SLC9A2 is correlation with lymphatic metastasis and poor survival in breast cancer

Abstract Background: SLC9A2 encodes Na+/H+ exchanger 2 which is an essential solute carrier protein on the surface of multiple cells. The prediction potentials of SLC9A2 in lymphatic metastasis and survival were unknow but explored in this study of breast cancer. Methods: Expression of SLC9A2 was determined in breast cancers (n=127) using real time quantitative polymerase chain reaction. Transcript levels of this gene was analysed in the breast cancers for the implication in lymph node involvement and survival using Mann-Whitney test with SPSS (Version 27). The relation of prognosis was also analysed by Kaplan Meier plotter in breast cancer. Results: In lymph node positive breast cancer, the expression of SLC9A2 shown an increase trend than no metastasis (n=43, median=25.9, interquartile range [IQR] [0.9-215.4] vs. n=44, median=4.9, IQR [0.2-31.8], p=0.1213). SLC9A2 expression in TNM stage Ⅱ was significantly higher than stage Ⅰ (n=31, median=42, IQR [0-195] vs. n=47, median=3.3, IQR [0.2- 31.6], p=0.0267) and also showed in the pathological type of invasive ductal carcinoma (n=27, median=42, IQR [3- 550] vs. n=35, median=3.3, IQR [0.2-31.8], p=0.0223). Kaplan Meier plotter showed over survival of SLC9A2 high expression was significantly worse than SLC9A2 low expression (66 months vs. 123.6 months, Hazard Ratio [HR]=1.57 [1.3-1.9], p=0.000), also found in estrogen receptor (ER) positive (63.8 months vs. 173.7 months, HR=2.19 [1.6-3.01], p=0.000). In patients with tamoxifen therapy, SLC9A2 high expression also had poor survival comparing to low expression (HR=2.86 [1.4-5.86], p=0.0026). Conclusions: High expression of SLC9A2 is correlation with lymph node metastasis and poor survival in breast cancer. SLC9A2 could be as a predictor for lymphatic involvement and survival and might be an indicator for detection of resistance to endocrine therapy. Citation Format: Binbin Cong, Xiaoshan Cao, Wen Jiang, Lin Ye. High expression of SLC9A2 is correlation with lymphatic metastasis and poor survival in 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 PO4-05-12.

Abstract PO3-01-13: A study of the impact of the implementation of the Oncotype Dx 21-gene breast-cancer assay during the SARS-CoV-2 pandemic for 1-3 node positive early breast cancer: The Clatterbridge Cancer Centre Experience

Abstract Background: The 21-gene breast cancer (BC) assay (Oncotype Dx) is used to predict chemotherapy benefit in ER+, HER-2- lymph node (LN) negative BC. The RxPONDER trial demonstrated that post-menopausal patients with ER+, HER2- BC with 1-3 LN and a recurrence score (RS) of &amp;lt; 25 did not benefit from adjuvant chemotherapy. In response to the SARS-CoV-2 pandemic Oncotype Dx was implemented for ER+, HER2- 1-3 LN+ BC patients in Merseyside, UK (population 2.6 million) This study sought to understand the impact of this measure on clinical practice. Methods: All patients whose tumours were assessed with Oncotype Dx assay between Mar 20 - Nov 22 were identified through the Exact Sciences portal. Menopausal status, tumour characteristics, RS and chemotherapy regimen were recorded. The impact on cancer care was estimated using the number of infusions and clinic visits specified by our institution chemotherapy protocol for node positive disease. The financial impact was calculated using the test list price, estimated costs of adjuvant chemotherapy in the UK (Annals of Oncology, Volume 32, suppl 2 S46). The number of patients predicted to receive chemotherapy pre-oncotype DX was calculated using data from the UK PONDx trial data. Results: A total of 242 patients were tested over the 32 month period. Table 1 summarises the clinico-pathological characteristics including by RS score. The median age was 58.5 and 77.3% (n=187) were post-menopausal. The median tumour size was 25mm and median LNs with macrometastasis was 1. 198 (81.9%) patients had an RS &amp;lt; 25. Overall 73 patients (30%) received chemotherapy of which 34 had an RS &amp;lt; 25. Pre-menopausal patients were more likely to receive chemotherapy with RS &amp;lt; 25 than post-menopausal patients, 47.9% (23/48) vs 7.3% (11/150) respectively. In the absence of Oncotype Dx testing 169 patients would have received adjuvant chemotherapy. Therefore, 96 patients avoided chemotherapy. This equates to 1,620 chemotherapy infusions and 324 clinic attendances. The estimated cost saving was ~£50K. Conclusions: This real-world study demonstrates that the use of Oncotype DX assay for ER+,HER2- 1-3 LN+ early BC spared a significant number of patients chemotherapy during the SARS-CoV-2 pandemic, so avoiding the risk of adverse effects. This also resulted in benefits to the healthcare system with a reduction in scheduled cancer care and achieved financial savings. This, therefore, demonstrates the benefit of using the Oncotype Dx assay. Table 1: Clinico-pathological information Citation Format: Alexandra Johnson, Sonia Bathla, Leena Chagla, Joanne Cliff, Allison Hall, Anita Hargreaves, Clare Hart, Zafar Malik, Chandeena Roshanlall, Raj Sripadam, Carlo Palmieri, Helen Innes. A study of the impact of the implementation of the Oncotype Dx 21-gene breast-cancer assay during the SARS-CoV-2 pandemic for 1-3 node positive early breast cancer: The Clatterbridge Cancer Centre Experience [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 PO3-01-13.

Abstract PO3-23-07: Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients

Abstract Background: Axillary surgery is now routinely de-escalated in clinically node negative breast cancer patients with limited axillary nodal burden (up to 2 involved sentinel nodes) based on the results of ACOSOG-Z0011 and AMAROS trials. However, patients with proven axillary metastasis following on ultrasound (AUS) guided core needle biopsy (CNB), undergoing primary surgery are still subjected to an axillary lymph node dissection (ALND) irrespective of the magnitude of the axillary nodal burden. If we could predict axillary nodal burden with a low false negative rate (FNR) for the presence of extensive axillary nodal involvement, we can then hypothesize that axillary surgery could be safely de-escalated in this cohort of patients. We investigated whether pre-operative AUS suggesting limited axillary burden is sensitive enough to rule out gross axillary disease burden. Methods: A single institution retrospective study. We undertook an electronic chart review of all T1 to T3 patients undergoing upfront ALND with either mastectomy or breast conserving surgery between January 2019 and June 2023. Patients with palpable axillary nodes, locally advanced breast cancer or a completion ALND after positive sentinel lymph node biopsy (SLNB) were excluded from the study. Clinical and pathological characteristics associated with nodal burden of disease were evaluated. Limited axillary burden was defined as &amp;lt; 2 involved nodes with ≥3 taken as gross nodal burden for primary analyses. Sensitivity analyses were carried out with limited axillary burden defined as &amp;lt; 3 involved nodes (N1) and ≥4 (N2) taken as gross nodal burden. Subgroup analyses in T1 or T2 tumors were carried out as well. The probabilities of discordant events, defined as limited burden on AUS-CNB but gross burden on final histopathology evaluation (HPE), assuming 10% FNR, were estimated using inverse cumulative binomial distribution function. Results: Data on the exact number of suspicious nodes on AUS were missing for 2 patients, therefore, the final study cohort included 39 patients. The correlation between AUS nodal burden and that on HPE was moderate (Spearman’s rho = 0.48; p = 0.0018). The sensitivity and specificity of AUS in identifying gross nodal burden were 61% and 81% respectively. Observation of 9 discordant events in 22 patients with low burden on AUS ruled out an FNR of &amp;lt; 10% with 99.99% certainty. The sensitivity and specificity in T1/T2 subgroup were 60% and 75% respectively. The sensitivity analyses classifying N1 as limited and N2 as gross axillary burden showed the sensitivity and specificity of 35% and 82% respectively and an FNR of &amp;lt; 10% was ruled out with 99.996% certainty. Conclusion: Pre-operative AUS alone lacks the sensitivity and specificity to accurately predict the true axillary nodal burden to safely guide de-escalation of axillary surgery. AUS followed by targeted axillary dissection (TAD) in conjunction with a dual technique SLNB may provide the desired sensitivity and specificity to guide de-escalation of axillary surgery. A prospective evaluation of this approach is merited. Given the limited number of patients that could be enrolled in such prospective study from individual institutions, an international collaborative effort is needed to address this important research question. Citation Format: Nidhi Garg, Mangesh Thorat, Hisham Hamed, Ashutosh Kothari. Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients [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 PO3-23-07.

Abstract PO5-22-12: Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial

Abstract Background: De-escalation of axillary surgery in patients with lymph node-positive breast cancer is currently being tested in ongoing trials for patients with downstaged nodes after neoadjuvant chemotherapy (NAC). A proportion of such patients will achieve an excellent axillary node response to NAC, i.e. conversion to pathologic node-negative status after chemotherapy. Genomic prediction of tumor chemosensitivity before final surgery may identify which patients could safely undergo conservative surgical management of their regional lymph nodes. Methods: The AGO-35 (NCT0203274) is a prospective trial for patients with HER2 negative breast cancer scheduled for neoadjuvant chemotherapy that includes an anthracycline- based regimen followed by 3-4 cycles of taxanes. The LN predictor is a newly developed model for predicting the probability of pathological lymph node-positivity after NAC in triple-negative (TNBC) or hormone-receptor positive (HR+) breast cancer. To calculate the LN predictor, which is developed in microarray, we calibrated the normalized individual gene module and SET ER/PR from RNAseq to the Affymetrix U133A platform using independently combined total of 220 pairs of TNBC samples with both RNAseq and U133A microarray results. The logistic regression model is applied for the prediction of the binary outcome, pathological lymph node-positive or negative after NAC. The cut-points of LN predictor in TNBC and HR+ samples were pre-determined for each subtype of breast cancer and then, independent, blinded evaluation in the AGO-35 trial samples. Results: A total of 251 patients with HER2 negative breast treated with neoadjuvant chemotherapy were included. The LN predictor was validated on 189 qualified samples with wtRNA sequence. Statistical analysis of 181 samples is shown in Table 1. Conclusion: Preliminary results of the AGO-35 trial show that the newly developed molecular LN predictor may accurately predict chemosensitivity response to NAC, in high proportion of patients with TNBC. Supported by: Wissenschaftsfonds (FWF) KLI 406 EUBREAST study group AGO Österreich Breast Cancer Research Foundation (BCRF-0158) Table 1. Genomic prediction of chemosensitivity Citation Format: Florentia Peintinger, Thorsten Kühn, Hans-Christian Kolberg, Roland Reitsamer, Sabine Schmatloch, Elisa Sieghartsleitner, Lili Du, Andrea Berghold, W. Fraser Symmans. Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial [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 PO5-22-12.

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 PO2-02-03: Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country

Abstract INTRODUCTION: Oncotype DX® recurrence score (ODX RS) is a 21-gene assay warranted to determine the the prognosis in patients with hormone receptor positive, HER-2 negative early stage breast cancer. In this context, the test is also predictive of benefit of adjuvant chemotherapy.1,2,3 OBJECTIVES: We aimed to correlate the clinical and pathological factors associated with Oncotype DX® 21-Gene in patients diagnosed with early stage Breast Cancer. Additionally, description of adjuvant treatment patterns and survival outcomes were described according to the Oncotype DX® 21-Gene result. METHODS: Data from medical records from a single center in Brazil were collected retrospectively from women over 18 years diagnosed with early breast cancer between 2012 and 2022. Included patients were diagnosed with stage T1-T2 breast cancer, hormone receptor positive, HER-2 negative, with up to three positive lymph nodes. All included patients had an Oncotype DX® test performed after definitive breast surgery. The ODX RS has been categorized into two levels according to menopausal status. Correlation between breast cancer recurrence and clinicopathological characteristics was done. The software SPSS was used for statistical analyzes with the significance of 0.05. RESULTS: From 197 patients, 20 have had breast cancer recurrence (10.15%) whom 10 were premenopausal and 10 were postmenopausal. The median ODX RS in these 20 patients was 15 (ranged from 9 to 31). The most common site of recurrence was breast and regional recurrence in 18 patients (90%). Adjuvant chemotherapy was omitted in 16 patients (80%) who have had breast cancer recurrence. Among premenopausal patients whose ODX RS was &amp;gt;20, 33 patients (91.66%) received adjuvant chemotherapy. Among postmenopausal patients whose ODX RS was &amp;gt;25, 19 (86.36%) received adjuvant chemotherapy. The probability of recurrence free survival was worse in premenopausal patients &amp;gt; 44-years-old compared to those with &amp;lt; =44 years-old (p = 0.036) and also worse in histological grade 3 tumors compared to grade 1 (p=0.0048). Tumor size &amp;gt;14 millimeters (mm) was correlated to worse recurrence free survival in premenopausal patients (p=0.017). Low estrogen and progesterone receptor was associated with a higher ODX RS (p=0.0035 and p&amp;lt; 0.0001, respectively) in premenopausal patients, but not associated with recurrence free survival. Clinicopathological characteristics and recurrence free survival correlation in postmenopausal patients were not significant. CONCLUSION: This retrospective analysis suggests that factors other than the Oncotype DX® score, such as age and grade contributed to worse survival outcomes among our patients population. Of note, age older than 44 years-old, histological grade 3 and tumor size &amp;gt;14 mm were associated with a higher probability of recurrence in premenopausal patients, despite the Oncotype DX® score. REFERENCES: 1. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med [Internet]. 2004;351(27):2817–26. Available from: http://dx.doi.org/10.1056/NEJMoa041588. 2. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med [Internet]. 2018;379(2):111–21. Available from: http://dx.doi.org/10.1056/NEJMoa1804710. 3. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med [Internet]. 2021;385(25):2336–47. Available from: http://dx.doi.org/10.1056/NEJMoa2108873. Table 1 – Clinical and pathological characteristics of 197 hormone receptor positive, HER-2 negative early breast cancer patients who did the Oncotype DX® 21-Gene Recurrence Score assay. Data from medical records collected retrospectively of women diagnosed with early breast cancer between 2012 and 2022 from a single center in Brazil. Figure 1 – Probability of recurrence free survival in premenopausal patients according to age &amp;lt;=44 (blue line) or &amp;gt; 44-years-old (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Figure 2 – Probability of recurrence free survival in premenopausal patients according to histological grade. Tumor with histological grade 1 (blue line) or histological grade 3 (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Citation Format: Carolina Cavalcanti Gonçalves Ferreira, Julio Araujo, Shermann Brandão Rodrigues Moreira, Antônio Buzaid, Débora Gagliato. Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country [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 PO2-02-03.

Abstract PO1-23-01: A novel nomogram for predicting the possibility of omitting axillary lymph node dissection after neoadjuvant chemotherapy for clinical node-positive breast cancer

Abstract Purpose: Currently, there is no validated strategy established for omitting axillary lymph node dissection (ALND), when axillary node metastases are expected to disappear with neoadjuvant chemotherapy (NAC) for clinical node-positive (cN+) breast cancers. In contrast, it was reported that the axillary pathological complete response (pCR) rate to NAC for cN+ breast cancer is approximately 40%. Therefore, it is necessary to develop a more accurate method for predicting nodal pCR (ypN0) to select patients who can omit ALND after NAC for cN+ breast cancer. Methods: This is a single-centered, retrospective clinical study conducted in 128 patients with cN+ primary breast cancer who underwent ALND after NAC between January 2014 and July 2021 at Saitama Medical Center. Clinical complete response (cCR) was defined as the disappearance of the primary tumor or axillary node metastasis, as confirmed by the findings of imaging. The pCR was defined as the absence of microscopic evidence of residual invasive carcinoma in primary breast tumor or axillary nodes. Clinicopathological variables were compared using Fisher’s exact test or logistic regression, as appropriate. Statistical significance was set at p&amp;lt; 0.05. Results: The median age of the patients was 52 years; 48.4% were premenopausal, 38.3% had cT3 or higher, 22.7% had cN2 or higher, and 50% had stage III disease. Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) positivity accounted for the patients were 58.6%, 50%, and 31.3%, respectively. NAC included sequential taxanes and anthracyclines in 47.7% of the patients, and anti-HER2 therapy was used in all patients of HER2-positive breast cancer. Breast primary tumor cCR (ypT0) was 29.7% and ypN0 was 44.5%. The ypN0 rate was 19.5% higher than the ypT0 rate in all patients (p &amp;lt; 0.001); it was 4.8% higher in the luminal subtype (p=0.009), 25.5% higher in the triple-negative subtype (p &amp;lt; 0.001), and 29.3% higher in the HER2 subtype (p=0.015). Additionally, the ypN0 rate was 3.9% higher than the axillary node cCR (ycN0) rate in all patients (p &amp;lt; 0.001), 7.6% lower in luminal type (p &amp;lt; 0.001), 13.6% higher in triple-negative type (p &amp;lt; 0.001), and 5% higher in the HER2 subtype (p=0.006). When ycN0 was predicted to be ypN0, the negative predictive value (NPV) was 77.2% and the false negative rate (FNR) was 19.7% (Table 1). In the association between ypN0 and preoperative clinico-pathological factors in cN+ breast cancer treated with NAC, univariate analysis showed significant differences in ER negativity (ER-) [hazard ratio (HR): 0.186, 95% confidence interval (CI): 0.086–0.401, p&amp;lt; 0.001], PgR negativity (HR: 0.360, 95% CI: 0.176–0.736, p=0.005), HER2 positivity (HER2+) (HR: 4.394, 95% CI: 1.941–9.949, p&amp;lt; 0.001), ycT0 (HR: 10.667, 95% CI: 4.020–28.304, p&amp;lt; 0.001), and ycN0 (HR: 9.966, 95% CI: 4.399–922.576, p&amp;lt; 0.001). The multivariate analysis revealed that ER, ycT0, and ycN0 were independent predictive factors for ypN0 after NAC in the patients with cN+ breast cancer (Table 2). These independent factors in multivariate analysis were used to create a nomogram for ypN0 prediction. The points added were 82 if the patient was ER-, 56 if the patient was ycT0, and 100 if the patient was ycN0, and the total of these scores was used to predict whether the patient had ypN0. When the Receiver Operating Characteristic curve was used to determine the cut-off value of the total points, 119 or more points were predicted to be ypN0, the NPV was 92.9%, and the FNR was 4.5%, which demonstrated an approximately 15% improvement over the prediction of ypN0 by ycN0 alone (Table 3). Conclusion: ER, ycT0, and ycN0 are independent predictive factors of ypN0 in cN+ breast cancer, suggesting that ypN0 prediction using a nomogram may contribute to individualized axillary treatment. Table 1. Accuracy of ypN0 prediction with ycN0 after NAC for clinical node-positive breast cancer Table2. Univariate and multivariate analyses of the relationship between preoperative clinicopathological factors and pathologically axillary node-negative after neoadjuvant chemotherapy in clinical node-positive breast cancer Table 3. Accuracy of ypN0 prediction after NAC for clinical node-positive breast cancer using Nomogram Citation Format: Hirohito Seki, Yuki Ishiguro, Ken Shimizu, Akitsugu Makino, Yoshiharu Ishizaka, Ai Tsuchiya, Hirotsugu Isaka, Shigeru Imoto. A novel nomogram for predicting the possibility of omitting axillary lymph node dissection after neoadjuvant chemotherapy for clinical 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 PO1-23-01.

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 PO2-19-02: NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET)

Abstract Background: Identifying pts with HR-positive/HER2-negative breast cancer (BC) who benefit from adjuvant chemotherapy (ACT) has been a major research focus over the past 20 years. Development and clinical application of genomic classifiers such as the 21-gene recurrence score (RS) has contributed to the biologic understanding of BC and has refined pt selection for ACT. The TAILORx and RxPONDER clinical trials demonstrated that RS identifies many postmenopausal pts with node-negative and node-positive BC and RS &amp;lt; 25, who do not benefit from the addition of ACT to endocrine therapy (ET). However, both trials also showed that certain subsets of premenopausal pts (node-negative/high clinical risk/RS 16-20, node-negative/RS 21-25, and node-positive/RS &amp;lt; 25) benefited from the addition of ACT to ET. Most premenopausal pts in these two trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR-positive/HER2-negative BC in the SOFT and TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, OFSET is a Phase III, multicenter clinical trial evaluating the addition of ACT to OFS+ET vs. OFS+ET alone. Methods: We hypothesize that the addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR-positive/HER2-negative tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival (IDFS), overall survival (OS), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and health-related quality of life (HRQOL). Eligible pts must be node-negative with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS &amp;lt; 25. Stratification is by nodal status/RS status (pN0 RS 16-25 vs pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 vs ≥40). Pts are randomized after surgery to either OFS+ET or ACT followed by OFS+ET. ET is an aromatase inhibitor per investigator discretion, but tamoxifen is allowed if pts do not tolerate the AI or if OFS is incomplete. Radiation therapy will be administered per investigator discretion according to protocol guidelines. The HRQOL sub-study will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score, between the arms, as well as increased pain severity (PROMIS) during ACT+OFS+ET compared to OFS+ET. Blood and tumor specimens will be collected for future research. The accrual of 3,960 pts is anticipated to be completed in seven years and seven mos. Based on data from NSABP B-28 and RxPONDER, the 5-year IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on data from TAILORx, the 5-year IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of the pts to be pN0 and 44% pN1, a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET vs. OFS+ET, with one-sided alpha of 0.025 and 80% power will require 380 IBCFS events, which are expected to occur ~11 years after study initiation. The OFSET study is expected to be activated in the third quarter of 2023. Current accrual (06-19-2023) is 0/3,960 Support: U10CA180868, U10CA180822, UG1CA189867, U24CA196067. NCT05879926. Citation Format: Eleftherios Mamounas, Gong Tang, Shannon Puhalla, Sandra Swain, Patricia Ganz, N. Lynn Henry, Reena Cecchini, Sonya Reid, Priya Rastogi, Charles Geyer, Julia White, Amy Clark, Tufia Haddad, Gregory Vidal, Norman Wolmark. NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET) [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 PO2-19-02.

Abstract PO4-17-12: Early adherence to adjuvant abemaciclib: Data from the Belgian Medical Need Program

Abstract Patient adherence profiles for adjuvant hormonal therapy combined with abemaciclib in HR+/HER2- High Risk EBC based on real world evidence (RWE) from a Medical Need Program in Belgium Background Following results of MonarchE, demonstrating clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), a 2-year treatment with abemaciclib has been reimbursed in Belgium since May 1st, 2023 for the adjuvant treatment of HR+, HER2–, lymph node-positive (&amp;gt;3 or 1-3 if pT3 or grade 3) early breast cancer (EBC). In this trial, adverse event related treatment discontinuation was reported in 18,5% (8.9% after dose reduction) of which 10.1% in the first 5 months after starting this CDK 4/6 inhibitor. Prior to reimbursement, an early access program was initiated in Belgium on June 28 2022. We studied the proportion of patients estimated to be eligible for the program nationwide who effectively started adjuvant abemaciclib, as well as early treatment discontinuation and dose reductions. Methods The number of eligible patients for the adjuvant abemaciclib Medical Need Program (MNP) was estimated by the Belgian Cancer Registry based on the above mentioned reimbursement criteria for patients registered during the incidence year 2018. The MNP was active in Belgium from June 28 2022 until May 1 2023. Discontinuation rate and proportion with dose reductions were calculated using a nationwide prospective managed monthly updated register of participating patients including information on age at diagnosis, time since therapy start, delivered doses and patient reported adverse events (AE). They all signed an informed consent and agreed to share their registered data after anonymization. Data analysis was retrospective. Descriptive statistics were used. Results In this 10-month period, 840 patients were estimated to be eligible to receive adjuvant abemaciclib in Belgium. A total of 311 patients (309 women, 2 men) were included in the program, 37% of the estimated number of patients. Median age at initiation was 57 y. Median time on treatment was 4.5 months (156 patients &amp;gt;4.5 months on treatment). 21/311 (6.7%) patients discontinued (all causes). 2 patients never started. 10 patients (3.2%) discontinued their therapy without dose reduction. 12/311 (3.8%) had a starting dose of 2 × 100 mg/d. 128/311 (41.1%) had a dose reduction, 96/128 (75%) before 3 months of therapy. In the subgroup of 156 patients starting treatment &amp;gt;4.5 months ago, 16/156 (10.2%) discontinued treatment, 13 patients have not yet been reported. 79/156 (50.6%) required a dose reduction, of which 7 (4.5%) discontinued after dose reduction. The reasons for discontinuation reported: 8/21 (38%) gastro-intestinal intolerance, 3/21 (14.2%) real deterioration in renal function, 8/21 quality of life issues (not specified), 1/21 anal burning sensation and anal fistula, 3/21 asthenia and fatigue. Conclusion Of the estimated eligible patients in Belgium 37 % started with adjuvant abemaciclib. These results illustrate that there is a need to further improve implementation of adjuvant abemaciclib. Early results show that 89.8% of patients receiving adjuvant abemaciclib therapy in Belgium continued their treatment after 4.5 months and 50% of patients needed a dose reduction. Longer follow-up will be needed. Understanding the reasons of discontinuation and early dose adjustments can enable better patient support on adherence. This is a critical capability to ensure optimal patient compliance. Citation Format: Maxime Van Houdt, Marc Michaux, Sevilay Altintas, Ahmad Awada, Jean-Luc Canon, Hannelore Denys, François Duhoux, Guy Jerusalem, Jeroen Mebis, Rosanne Janssens, Isabelle Huys, Barbier Liese, Charlotte Verbeke, Sileny Han, Hans Wildiers, Patrick Neven. Early adherence to adjuvant abemaciclib: Data from the Belgian Medical Need Program [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 PO4-17-12.

Abstract PO5-02-14: Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients

Abstract Introduction: The long-term severe adverse events associated with anthracyclines, including irreversible cardiotoxicity, myelodysplastic syndromes, and therapy-related leukemias, led researchers to question the risk-benefit of anthracycline-based chemotherapy regimens, especially for patients without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Docetaxel plus cyclophosphamide (TC) has replaced doxorubicin plus cyclophosphamide (AC) for lower-risk patients that need adjuvant chemotherapy. However, the optimal number of cycles of adjuvant in patients with node-positive or node-negative breast cancer is currently unknown. Methods: We performed a retrospective cohort study of patients with HER2-negative breast cancer, stage I to III, that received adjuvant docetaxel and cyclophosphamide (TC) for four or six cycles, treated from January 2010 to December 2021. Patients were included from four cancer institutions, both private and public, located in the South, Southeast, and Northeast of Brazil. Objectives: To investigate the clinical-pathological characteristics and survival of earlystage HER2-negative breast cancer patients who received four (TC4) or six cycles (TC6) of adjuvant docetaxel and cyclophosphamide (TC). Results: We collected data from six hundred and ninety-eight patients, 98.7% were female with an average age of 52 years, 51.9% were postmenopausal, 14.6% BRCA gene mutation, 66% had some comorbidity, and only 8.4% were not candidates for anthracyclines. Two hundred and twenty-five patients had public and 473 private health insurance. About 13.2% of the patients were hormone receptor negative (HR-) and 86.8% hormone receptor positive (HR+), 57.4% breast-conserving surgery and 77.7% sentinel lymph node (SL). Five hundred sixty-four (80.8%) patients received TC4 and 134 (19.2%) TC6. We observed that patients who received TC 6 had unfavorable prognostic factors such as: (TC4 vs TC6) previous breast cancer (8.7% vs 16.3%) (p=0.002), invasive ductal carcinoma (IDC) (73.4 vs 86.7%) (p=0.009), histological grade 3 (HG3) (34.9 vs 42.9%) (p= 0,085) conservative surgery (59.4% vs 53%) (p=0144), SL (80.9% vs 62.2%) (p =0.001), Lymph node positive (15% vs 42.3%) (p=0.001), pathological stage II (37.5% vs 50%) (p=0.001).Treatment completion rates were 96.5% and 84.3% for TC4 and TC6, respectively (p=0,02). The incidence of grade 3 or higher toxicity with TC6 (14% vs 21.1%; p= 0,043). Febrile neutropenia was observed in 6.7% of both groups. Grade 3 or higher neuropathy was most common with TC6 (2.2% vs 10.3%; p=0,163). Permanent treatment discontinuation was more frequent in the TC6 group (3.4% vs. 9.8%; p=0,004), as well as late toxicity (3.4% vs. 9.2%; p=0,004). Ninety-four percent of the patients completed the proposed cycles of chemotherapy, 72% received adjuvant radiotherapy and 85.4% received adjuvant hormone therapy, with 42% of these receiving an aromatase inhibitor for 5 years. The median follow-up of the entire cohort was 61 months. There was no difference in the 5-year DFS (77.5% vs. 64.7%; p=0.159) or the 5-year OS (89.5% vs. 70.5%; p= 0,06) between patients treated with TC4 and TC6. Conclusion: TC6 was commonly used for patients with unfavorable prognostic factors as history of previous breast cancer, (IDC), HG III, lymph node positive and stage II. Patients who received TC6 had less chance of completing the treatment and more severe toxicity, especially late peripheral neuropathy. There was no difference in DFS or OS. Citation Format: Mila Kraychete, Marcelle Cesca, Guilherme Almeida, Leonardo Santana, Luciana Leite, Solange M. Sanches, Vladmir Cordeiro de Lima, Rafaela Pirolli, Rafael Manea, Felipe Kaneta, Jean Coutinho, Lucas Vian, Waires Zeviani, Marcio Reis, Luciana Landeiro, Clarissa Mathias, Geila Nunez, Tamara Santana, Monique Tavares. Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients [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 PO5-02-14.

Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument

Abstract Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient. Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [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 Db1-01.

Abstract PO4-22-10: Prognostic impact of preoperative lymph node diagnostic tools for patients with suspicious node positive breast cancer

Abstract (Abstract) Recently, the SOUND trial demonstrated the feasibility for omission of sentinel lymph node biopsy (SNB) in cases with negative ultrasound (US)-guided fine-needle aspiration cytology (FNA) of suspicious lymph nodes (LNs). An important consideration for omission of SNB depends on a highly accurate assessment of preoperative staging for axillary LNs. (Purpose) The purpose of this study was to investigate the impact of preoperative diagnostic tools for axillary lymph nodes (LNs) staging of early breast cancer. (Materials and Methods) A total of 3088 consecutive patients with operable breast cancer were retrospectively identified at our institution between April 2013 and March 2020. Patients with suspicious axillary LN of breast cancer were assessed using preoperative US and computed tomography (CT), underwent FNA or core needle biopsy (CNB). The inclusion criteria for both FNA and CNB were a cortical thickness [3 mm or abnormal morphological characteristics. Patients with biopsy-proven metastasis underwent axillary lymph node dissection (ALND), and those with a negative FNA or CNB underwent SNB. If the SNB was positive, ALND was performed. Diagnostic accuracy for SNB was calculated for both FNA and CNB. In addition, the patients in this study were divided into two groups as follows: the cN0-FNA negative group (suspicious LN but negative FNA) and the cN0-CNB group (suspicious LN but negative CNB). Overall survival (OS)and invasive disease survival(iDFS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. (Results) A number of patients with negative or suspicious metastasis US/CT findings of LNs were 3187, with 963 undergoing FNA and 395 undergoing CNB for suspicious LNs. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 63, 99, 99, 73, and 81% in FNA, and 87, 100, 100, 91 and 95% in CNB, respectively. SNB was performed in 207 (cN0-CNB group) of 395 CNB and 581 (cN0-FNA group) of 963 FNA patients. Two hundred and seven patients from the cN0-CNB group (T1ab; 42, T1c; 72, T2;84, T3;9 patients) treated with SNB were compared to 581 from the cN0-FNA group (T1ab;86, T1c;193, T2;278, T3;24 patients) in terms of number of LN metastasis. A number of patients with micrometastases, 1,2,3 or more than 4 positive LNs were 5(2%),7(3%),3(1%)9,3(1%) and 0 (0%) in cN0-CNB group, and 23(4%),67(12%),26(4%),12(2%) and 29 (5%) in cN0-FNA group, respectively. The significant difference in 5ys iDFS and OS was observed between CNB group and FNA group (94.2% vs.91.4%, p =0.04 and 99% vs. 95%, p=0.004, respectively). Conclusions The preoperative diagnosis of axillary LNs was influenced by the diagnostic tool used. CNB is a reliable method for the preoperative diagnosis of LN metastasis. The prognosis of early breast cancer with clinically metastasis-negative lymph nodes diagnosed by CNB is better than that by FNA. Table. Number of positive lymph nodes cN0-FNA (%) cN0-CNB (%) Total 207 100 581 100 0 189 91 424 73 micrometastasis 5 2 23 4 1 7 3 67 12 2 3 1 26 4 3 3 1 12 2 4 more than 0 0 29 5 Citation Format: Rikiya Nakamura, Shouko Hayama, Rikiya Nakamura, Naohito Yamamoto. Prognostic impact of preoperative lymph node diagnostic tools for patients with suspicious 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 PO4-22-10.