Breast Cancer Skip Metastases: Frequency, Associated Tumor Characteristics, and Role of Staging Nodal Ultrasound in Detection

BACKGROUND. Staging nodal ultrasound (US) evaluates locations beyond those assessed during routine surgical dissection and has an increasing role in breast cancer management given the growing use of neoadjuvant systemic therapy before surgical staging. OBJECTIVE. The purpose of this study is to identify the patterns of nodal spread of breast cancer observed at staging nodal US and to determine the frequency of skip metastases and associated tumor characteristics. METHODS. This retrospective study included 1269 consecutive patients (31 with bilateral synchronous cancers) who had 1300 newly diagnosed, untreated, invasive breast cancers and underwent US examination of the ipsilateral regional nodal basins from January 2016 through March 2017. Cases with suspicious nodes on US underwent fine-needle aspiration (FNA) biopsy. Cases with benign results on FNA and no suspicious nodes on US underwent sentinel lymph node biopsy. Results of US with FNA were compared with final surgical pathology. Skip metastases were defined as spread across discontiguous nodal levels or distant metastases in the absence of ipsilateral nodal metastases. The incidence and patterns of spread of skip metastases were summarized; associations with tumor characteristics were tested using the Fisher exact test. RESULTS. A total of 591 metastatic cases (45.5%) were confirmed by needle biopsy or sentinel lymph node biopsy, comprising 463 nodal metastases (N+) confirmed by FNA, 121 nodal metastases (N+) confirmed by sentinel lymph node biopsy, and seven distant organ metastases without nodal metastases (N0M1) confirmed by CT-guided biopsy. US with FNA had sensitivity of 86.0%, specificity of 100.0%, PPV of 100.0%, NPV of 89.5%, and accuracy of 93.6%. There were 34 skip metastases, for an incidence of 2.6% (34/1300) (95% CI, 1.8-3.6%) among all invasive cancers and 7.2% (34/470) (95% CI, 5.1-9.9%) among metastatic cancers detected by US and FNA. Skip metastases occurred to axillary level III (n = 4), the supraclavicular nodal basin (n = 21), the contralateral axilla (n = 2), and distant organs (n = 7). Cancers with skip metastases, compared with those with nonskip metastases, had higher rates (p = .005) of lobular histology (23.5% vs 6.7%) and mixed ductal and lobular histology (11.8% vs 6.7%). Skip metastases were not associated with grade, T category, or molecular subtype (p > .05). CONCLUSION. Skip metastases to locations beyond standard surgical axillary dissection occur in 7.2% of metastatic breast cancers. CLINICAL IMPACT. Staging nodal US identifies skip metastases that otherwise would be undetected, helping to achieve more accurate staging and minimize undertreatment.