Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer

Objectives

To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs).

Materials and methods

Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis.

Results

One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs.

Conclusion

Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making.

Trial registration

This trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020.

Critical relevance statement

A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer.

Key points

• CEUS can help identify and diagnose SLN in early breast cancer preoperatively.

• Combining lymphatic and grayscale US findings can predict axillary tumor burden.

• The nomogram showed a high diagnostic value in validation cohorts.

Graphical Abstract