Background: The American College of Surgeons Oncology Group Z0011 prospective randomized trial demonstrated no local control or survival advantage with more extensive axillary surgery, even in the setting of known axillary disease. These results convincingly showed that axillary surgery provides little, if any, therapeutic benefit. Given that axillary surgery is not associated with local control or survival benefit, the current role of sentinel lymph node (SLNB) is limited to staging the axilla (in other words, SLNB provides staging information but is not therapeutic).

Objectives: In this randomized, controlled non-inferiority trial we aim to determine the utility of axillary ultrasound (AUS) as a pre-operative staging modality for patients with clinically node-negative invasive breast cancer with the hope that it will be a minimally invasive replacement for SLNB.

1. Primary Objective: To assess whether axillary recurrence rates for patients randomized to Arm 1 (no SLNB) is equivalent to axillary recurrence rates for patients randomized to Arm 2 (SLNB).

2. Secondary Objective: To assess disease-free survival in Arm 1 vs. Arm 2.

3. Tertiary Objective: To assess overall survival in Arm 1 vs. Arm 2.

Study Design: A randomized non-inferiority trial comparing no further axillary staging versus SLNB in women with clinical T1-T2, N0 M0 breast cancer and negative AUS. Following a negative AUS, four hundred sixty women will be randomized in a 1:1 fashion to no further axillary staging or SLNB. Subjects will be monitored for local-regional and distant recurrence per NCCN guidelines. We have recruited 28 study participants.

Eligibility Criteria: To be eligible the patient must be 18-y.o. or older; female; have tissue-diagnosis of invasive breast cancer; cT1-2N0M0 cancer; negative AUS; ECOG </=2; available for follow-up; candidate for SLNB. A patient is ineligible if pregnant or lactating; has concurrent invasive bilateral breast malignancies or multicentric disease or is considered a poor surgical candidate.

Statistical Methods:

Power analysis: A power analysis was performed to determine the accrual goal. The power analysis is based on axillary recurrence, our primary endpoint. We expect an axillary recurrence rate of 1% in patients undergoing SLNB. By assuming a noninferiority limit of 2% difference, our sample size will allow us 80% power at 1-sided 0.1 significance level to assure such a noninferiority.

Data analysis: Longer-term formal data analysis for the study will be performed following the intent-to-treat (ITT) principle. Demographic and clinical characteristics of the sample, as well as efficacy, complication rates and loss to follow-up will be summarized using descriptive statistics. The balance of demographic and baseline clinical characteristics between two arms will be compared using t-test, Mann-Whitney rank-sum test, or Chi-square test as appropriate. The differences in OS and DFS between treatment arms will be compared using log-rank test.

Citation Format: Natalia S Tucker, William E Gillanders, Timothy Eberlein, Rebecca Aft, Julie Margenthaler, Feng Gao, Catherine Appleton, Imran Zoberi, Ademuyiwa Foluso, Amy Cyr. A prospective, randomized trial of sentinel lymph node biopsy versus no additional staging in patients with T1-T2 invasive breast cancer and negative axillary ultrasound [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-5-01.