Abstract PO4-19-07: Tailored Axillary Surgery (TAS) in Patients with Clinically Node-Positive Breast Cancer in the Upfront Surgery Setting: A Prospective, Single-Arm, Multicenter Trial

Abstract A brief background discussion: Axillary lymph node dissection (ALND), which can induce lymphedema, has been omitted in clinically node-negative(cN0) patients with positive sentinel lymph nodes (SLNs) if they meet the eligibility criteria of ACOSOG Z0011. Furthermore, the omission of ALND has been attempted through targeted axillary dissection (TAD) in patients whose clinically node-positive(cN+) status converts to ycN0 after neoadjuvant chemotherapy. However, ALND remains the standard of care in patients with cN+ who undergo upfront surgery. Trial design: This is a prospective, single-arm, multicenter phase II feasibility trial with the participation of 41 hospitals belonging to the breast cancer study group of Japan Clinical Oncology Group (JCOG). Tailored axillary surgery (TAS) removes labeled lymph node (LN) with clip, wire, or tattoo, palpable LNs, and SLNs. ALND is performed after TAS. These LNs removed by ALND other than TAS are defined as non-TAS LNs. Eligibility criteria: The eligibility criteria are as follows: 1) histologically-proven invasive breast cancer, 2) upfront surgery is planned, 3) pathologically diagnosed metastatic LN (cytology or core needle biopsy), 4) 1-3 LN metastases in level I by imaging, 5) cT1-3, and 6) females aged ≥18 and ≤74 years on the enrollment date. Specific aims: This trial aims to establish a surgical method of tailored axillary surgery (TAS) among patients with cN+ who undergo upfront surgery and to determine the appropriate criteria for the next phase III TAS trial, which omits ALND by TAS safely. The primary endpoint is the non-TAS LNs positive rate. Clinicopathological factors (the number of suspected metastases by imaging, the number of metastases in LNs resected by TAS, tumor size, and invasive ductal/lobular carcinoma) are analyzed to predict the non-TAS LN metastasis rate (e.g., 10%). The secondary endpoints are the TAS LNs identification rate, marked LN resection rate, arm edema incidence rate, and QOL (FACT-B, QuickDASH). Statistical methods: In this trial, among the combinations of factors involved in treatment selection, the objective is to narrow down the combinations that will result in a non-TAS metastasis-positive rate of less than 10% when TAS is performed. For a single combination, 167 cases need to be considered to reject a non-TAS metastasis-positive rate of 10% or more (5% one-sided alpha error, 70% power, and 5% expected value). However, performing these studies for all combinations lacks feasibility. Therefore, we decided to improve the estimation accuracy by using a regression model with the non-TAS metastasis-positive rate as the outcome variable and the factors involved in treatment selection as explanatory variables and to search for combinations of factors with a non-TAS metastasis-positive rate less than 10%. Based on the rule of thumb that a sample size of at least ten times the number of factors is required when using regression methods, a regression model is used when 60 cases are accumulated. The combinations with a 90% confidence upper limit of less than 10% of non-TAS metastasis positivity as the predictive value of the regression model will be selected as candidate combinations that fulfill the conditions. If the accuracy of the predictive value is considered insufficient, 60 cases will be added sequentially up to a maximum of 300 cases. Present accrual and target accrual: The patient recruitment was started in April 2023. Up to 300 patients will be enrolled over a 2-year recruitment period. Twenty-one patients were already enrolled until July 2023. Citation Format: Kaori Terata, Yasuaki Sagara, Tadahiko Shien, Takehiko Sakai, Shin Takayama, Dai Kitagawa, Tsuguo Iwatani, Takahiro Tsukioki, Mami Ogita, Naoko Sanuki, Masayuki Yoshida, Hitoshi Tsuda, Seiichiro Yamamoto, Hiroji Iwata. Tailored Axillary Surgery (TAS) in Patients with Clinically Node-Positive Breast Cancer in the Upfront Surgery Setting: A Prospective, Single-Arm, Multicenter 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 PO4-19-07.