Optimal management of breast cancer with physical exam negative/radiological abnormal axilla

For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II-III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1-2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1-2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1-2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.