S3-1: Update of International Breast Cancer Study Group Trial 23-01 To Compare Axillary Dissection Versus No Axillary Dissection in Patients with Clinically Node Negative Breast Cancer and Micrometastases in the Sentinel Node.

Introduction and Study Design For patients (pts) with a metastatic sentinel node (SN), axillary dissection is standard treatment to achieve optimal locoregional control. However, for many pts the SN is the only positive node and for pts with minimal SN involvement, axillary dissection (AD) may be overtreatment. IBCSG Trial 23-01 was designed to determine whether AD is necessary in pts with minimal SN involvement (defined as one or more micrometastatic (≤2 mm) SNs) and tumor ≤5 cm. Consenting eligible pts were first registered; those with the requisite SN involvement were randomized to AD (group A) vs. no further axillary surgery (group B). The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and systemic disease-free survival (SDFS). The trial started in April 2001 and closed in February 2010. The accrual target was 1,960 pts to provide 90% power to detect non-equivalence if 5-year DFS was 64% for group B and 70% in group A. At closure 6,681 pts had been registered, with 934 randomized from 27 centers. The primary reasons for early closure were that projected time to complete accrual was too long, and the aggregate event rate at 30 months median follow up was much lower than anticipated. Baseline Characteristics and Treatment Mean patient age at entry was 54 years (range 26–81). More postmenopausal (56%) than premenopausal pts (44%) were randomized. Sixty-seven percent of pts had tumor 2.0 mm, and 2% were unknown. Most (96%) pts underwent lymphoscintigraphy, and 1 or 2 sentinel nodes were found in about 85%. A previous excision biopsy was performed in 16%. Conservative surgery was definitive treatment in 75%; the others received mastectomy. Adjuvant radiotherapy was performed in 89% of group A and 92% of group B. Outcomes On 25 May 2011, median follow was 49 months. There were 88 DFS events. Sites of first DFS event were breast cancer-related in 66 pts [local (8), contralateral breast (10), regional (6), and distant (42)], and non-breast cancer-related in 22 [second malignancies (17) and deaths without prior cancer event (5)]. Four-year DFS (± standard error) was 91% (±1.4%). Four-year competing risk cumulative incidences were 7.3% (±1.0%) for breast cancer events and 2.0% (±0.5%) for non-breast cancer events. With 101 DFS events, the trial is estimated to have 90% power to detect non-equivalence if 5-year DFS is 87% for group B compared with 92% for group A. Conclusion In this trial, restricted to clinically N0 with microscopic SN involvement, breast cancer recurrence and relapse rates are very low at a median follow-up of 4 years. The first comparison of outcomes between the two arms will be presented after a median follow-up of 5 years, when number of DFS events is anticipated to exceed 100. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S3-1.