Regional nodal irradiation in the setting of sentinel node biopsy

: The need for axillary lymph node dissection (ALND) in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. The role of axillary management in patients with sentinel lymph node biopsy (SLNB) negative or micrometastatic disease is well established after multiple trials demonstrated no survival benefit with the addition of ALND (NSABP B32, IBCSG 23-01, AATRM048); yet, there remains controversy in the management of SLNB positive disease. ALND has traditionally been the standard of care following positive SLNB, however, results from recent studies have identified that further surgical exploration of the axilla may be overtreatment in these patients. In order to de-escalate treatment, non-surgical options such as regional nodal irradiation (RNI) and neoadjuvant chemotherapy (NAC) have been increasingly explored. Trials evaluating the role of RNI following positive SLNB have suggested that RNI is non-inferior to ALND and provides superior outcomes with an improved toxicity profile (AMAROS, MA.20, EORTC 22922). NAC has been explored in the treatment paradigm in patients with locally advanced disease, however, the role of SLNB and RNI in this setting remains unequivocal. This review aims to provide an update on the role of RNI following SLNB in IBC using an evidence-based approach. Ongoing clinical trials will clarify the role of axillary management after NAC in cN1 patients. In the Alliance A011202 trial, the role of ALND versus axillary nodal irradiation is addressed. Patients with clinical T1–3, N1 breast cancer treated with NAC and subsequent positive SLNB are randomized to receive ALND or axillary nodal irradiation along with radiotherapy to the whole breast or chest wall. Both groups will receive radiotherapy to the supraclavicular fossa. Patients in the ALND arm will receive radiotherapy to the undissected axilla. The target accrual is 1,660 patients and the primary study endpoint is invasive breast cancer recurrence-free interval (IBC-RFI) (NCT01901094). The NSABP B-51/RTOG 1304 trial is investigating the role of RNI in the same patient population who achieve pCR at ALND following NAC. Patients who present with clinical T1–3 tumors and N1 disease who achieve pCR post NAC are randomized to receive axillary RNI versus no further axillary treatment. Patients who receive RNI will also receive radiation to the whole breast or chest wall. The target accrual is 1,636 patients with the primary study endpoint of IBC-RFI (NCT01872975).