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Can We Use MRI and US to Predict Axillary Node Response in Breast Cancer?

In patients with node-positive breast cancer, treatment usually involves neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery or mastectomy. NAC usually results in a reduced tumor burden, improved survival in patients with a pathologic complete response, and a greater possibility for conservation surgery in the breast or the axilla (1). In patients who are likely to achieve an axillary pathologic complete response, omitting axillary lymph node (LN) dissection in favor of sentinel LN biopsy prevents morbidity and complication such as nerve damage, hematoma, and lymphedema (2). Prior studies, including the American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) and the SENTINA (sentinel lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) trials (1,3), have attempted to determine if axillary LN dissection could be omitted in favor of sentinel LN biopsy in patients with node-positive breast cancer undergoing NAC. The false-negative rate of the ACOSOG Z1071 trial was 12.6% and the false-negative rate for the SENTINA trial was 14.2%, which was greater than the threshold value of 10% and was regarded as unacceptably high (1,3). Because of the high false-negative rate, axillary LN dissection has remained the standard approach for node-positive breast cancer after NAC. In this issue of Radiology, Kim et al (4) describe an imaging-based predictive model using MRI and US, along with nodal stage and molecular receptor status, that could distinguish axillary pathologic complete response (no evidence of micrometastatic or macrometastatic disease) from residual axillary metastatic disease. This imaging-based model performed well in this single-center retrospective study, with an area under the curve of 0.84 and 0.78 in the test and the validation sets, respectively (4). When this model was applied to patients with a risk score of 1 (who were least likely to have residual axillary metastatic disease), the false-negative rates ranged between 5% and 10%, lower than the false-negative rates for the ACOSOG Z1071 and the SENTINA trials (1,3,4). Axillary lymphadenopathy at US after NAC had the strongest independent association with residual axillary metastatic disease at surgery on multivariate analysis. Other independent predictors of residual axillary metastatic disease included clinical N2 or N3 stage, less than 50% reduction in the breast tumor size at MRI, Ki-67 negativity, hormone receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity (all, P , .05) (4). Kim et al (4) defined clinically node-positive breast cancer as either pathologically confirmed or clinically suspicious axillary LN metastases. The results may have been altered if all node-positive cases were proven by using cytologic or pathologic analysis. I believe that the model could be improved if the axillary assessments relied more heavily on US and less on clinical examination, because it is known that clinical examination may miss small or deep axillary metastases and clinical examination may find “suspicious” palpable findings that are shown to represent normal or reactive axillary LNs at US. In a study by Kuerer et al (5), 42 of 133 (32%) patients with breast cancer underwent NAC with axillary downstaging. The sensitivity of US in identifying residual axillary metastatic disease was significantly higher than that of clinical examination (62% vs 45%; P = .012) (5). In the study by Kuerer et al, the sensitivity of clinical examination (84%) was higher than that of US (70%), but the difference did not achieve statistical significance. Among 55 patients with negative results for cancer at US and clinical examination following NAC, 29 patients (53%) were found to have axillary metastatic disease on axillary LN dissection (5). In 28 of the 29 patients (97%), the amount of residual axillary metastatic disease was small: involvement by one to three LNs or only micrometastatic disease (measuring 2–5 mm in diameter) (5). As usual, there are caveats. All patients were treated with anthracycline and taxane–based NAC. Anti-HER2 agents were used in 96.7% of the HER2-positive cases. If all the HER2-positive cases were treated with anti-HER2 agents, then there may have been a slight alteration in the results. If residual axillary metastatic disease was suspected at US or clinical examination, then the patient underwent axillary LN dissection. All other patients underwent sentinel Can We Use MRI and US to Predict Axillary Node Response in Breast Cancer?