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

Abstract

Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for two reasons: 1) it predicts prognosis and guides medical therapy, and 2) it is a potential therapy for removal of disease in the axilla. This paradigm has now been called into question. Prognostic information is driven increasingly by tumor biology, and trials such as the ACOSOG Z0011 demonstrates removal of axillary disease is not therapeutic. Staging of the axilla has undergone a dramatic de-escalation; however, sentinel lymph node biopsy (SLNB) is still an invasive surgery and represents a large economic burden on the healthcare system. In this review, we outline the changing paradigms of axillary staging in breast cancer from emphasis on anatomic staging to tumor biology, and the evolving role of axillary ultrasound, bringing patients less invasive and more personalized therapy.

Keywords: ALND; SLNB; Z0011; axillary staging; axillary ultrasound; breast cancer.

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.

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.