Staging of the Axilla in Breast Cancer and the Evolving Role of Axillary Ultrasound

Figures & data

Figure 1 Overview of current algorithms for axillary staging in early stage breast cancer. SLNB is recommended for patients with a clinically negative axilla. If ≥ 3 sentinel nodes are positive, completion ALND is recommended. No further intervention is indicated for ≤ 2 sentinel nodes are positive. US guided FNA/CNB is recommended for patients with a clinically positive axilla. If FNA/CNB is positive, ALND is indicated. If FNA/CNB is negative, SLNB ± ALND is recommended. For patients with a positive FNA/CNB who undergo NAC, SLNB may be considered depending on response to treatment.

Figure 2 Ultrasound features suggesting metastatic involvement of axillary lymph nodes. Normal lymph nodes have a uniform hypoechoic cortex, central fatty hilum, and smooth margins. Features identified to be predictive of metastatic lymph node disease include increased cortical thickness (OR=3), fatty hilum loss (OR=27), increased diameter, and irregular margins (OR=3). While the features high odds ratios, they are not individually predictive of lymph node metastasis and have poor AUCs.

Figure 3 Restaging of the axilla after NAC. ALND has traditionally been recommended for patients with a clinically positive axilla and positive FNA/CNB. For patients who are treated with NAC, evaluation with AUS can help reduce the utilization of ALND and concomitant patient morbidity. Following NAC, AUS can be used to assess response to therapy, If the AUS is negative after NAC, SLNB is recommended with ALND reserved for patients with ≥ 2 positive sentinel lymph nodes.

Table 1 Summary of Current Trials Underway Evaluating the Utility of AUS in Breast Cancer Staging

Trial	Type	Arms	Endpoint	Inclusion	Exclusion
SOUND (NCT02167490) N=1560 (780 per arm)	Multicenter prospective randomized non-inferiority trial (Δ=2.5%)	Arm 1: SLNB ± ALND Arm 2: Observation	1°: DDFS 2°: Distant recurrences, axillary recurrences, disease free survival, overall survival, and quality of life measures.	Breast cancer ≤2 cm cN0 (negative AUS or US FNA) Candidate for BCS	Synchronous distant metastases Previous malignancy B/l breast cancer Multicentric or multifocal disease Previous primary systemic therapy Pregnancy or breast feeding Pre-operative pathological diagnosis of axillary node metastasis Pre-operative radiological evidence of suspicious nodes Psychiatric hx
INSEMA (NCT02466737) Goal of N=7095	Multicenter prospective randomized non-inferiority trial	1st random: Arm 1: Observation Arm 2: SLNB 2nd random (1–3 positive SLN): Arm 1: Observation Arm 2: Completion ALND	Invasive disease free survival (IDFS)	Breast cancer ≤5 cm cN0 (negative AUS or US FNA) M0 Planned BCS	Hx of malignancy in past 5 years Non-invasive breast cancer T3/T4 tumors Neoadjuvant chemotherapy Pregnant or lactating Multicentric tumors Planned intra-op RT or post-op partial breast RT alone
BOOG 2013-08 (NCT02271828) Goal of N=1644	Multicenter prospective randomized non-inferiority trial	Arm 1: SLNB ± ALND Arm 2: Observation	Regional recurrence rate (up to 10 years)	Invasive breast cancer T1-2 tumors cN0 with negative AUS or US guided FNA Planned BCS	cN+ disease Bilateral breast cancer, metastatic disease History of invasive breast cancer Previous axillary surgery or RT Pregnant or nursing Prior malignancies within past 5 years

Abbreviations: SLNB, sentinel lymph node biopsy; ALND, axillary lymph node dissection; AUS, axillary ultrasound; US, ultrasound; FNA, Fine Needle Aspirate; BCS, breast conservation surgery; RT, radiation therapy.

Figure 4 Possible future algorithm for staging of the axilla in early stage breast cancer. Several studies are currently ongoing evaluating the ability of AUS to accurately exclude disease in the axilla. If these studies are successful, the paradigm for axillary staging will evolve. Patients with newly diagnosed T1-2 breast cancer will be evaluated with an AUS. Patients with negative AUS will not require further axillary staging. Patients with a positive AUS will undergo FNA/CNB. Patients with a negative FNA/CNB can be observed. Patients with a positive FNA/CNB should undergo SLNB, possible ALND.