Neonod Study: Conservation of axillary lymph nodes in the presence of micrometastases in the sentinel lymph node if cN- After neoadjuvant chemotherapy

Background: In the last 20 years it was observed a clear trend to develop and perform less and less demolitive axillary surgery in breast cancer patients. The development of identification, dissection and intraoperative analysis of sentinel lymph node (SLNB, Sentinel Lymph Node Biopsy) contributed to give all informations on the need to proceed or not to axillary lymph node dissection (ALND), while neoadjuvant chemotherapy (NAC) permitted to enable surgical treatment in initially non-operable cancers or to reduce tumor size in order to perform a less demolitive surgery. In Patients with residual axillary disease after NAC, it is not completely clear if the prognosis worsens according to the entity of residual disease (isolated tumor cells or ITC, micrometastases, macrometastases). In particular, IBCSG 23-01 study demonstrated that, in patients with ypN1mi early breast cancer, axillary lymph node dissection (ALND) could be avoided without worsening the prognosis. Assuming that patients cN+ before, but ypN1mi after NAC are clinically equivalent to patients in IBSCG study, complete ALND would be useless even if in patients subjected to NAC for that subgroup. Still it is to demonstrate if axillary micrometastases after NAC could have a prognostic value similar to micrometastasis in patients subjected to adjuvant treatment. To overcome these limitations, we propose this non-controlled clinical study to verify the effect of avoiding ALND on relapse and survival rate in cN+ patients, turned ycN0 (clinically) and ypN1mi (pathologically) after NAC. Materials and methods: This is a non-controlled clinical study designed as a non-inferiority study to verify if the avoidance of ALND in ypN1mi patients after NAC does not involve a significant worsening of survival or locoregional or distant relapse risk compared to ypN0 patients, in which the avoidance of ALND actually represents the standard treatment. Patients with macrometastatic SLN (ypN≥1) after NAC subjected to ALND as a standard procedure represents an internal control group for the demonstrated worse prognosis compared to ypN0 and ypN1mi patients. This study includes patients with cN+ lymph nodes assessed in the initial diagnosis, resulted negative (with clinical and instrumental studies) after NAC. On the base of histopathologic definitive evaluation on harvested sentinel lymph nodes, patients will be allocated in one of the two groups (standard or experimental). Group 1 (experimental) will include patients with micrometastatic SLN or micrometastatic parasentinel lymph node (ypN1mi), in which ALND will not be performed. Group 2 (standard) will include patients with negative SLN or SLN with ITC in it (ypN0/ypN0(i+)). ALND will not be performed in these patients. Patients with macrometastatic SLN or another macrometastatic lymph node (ypN≥1) will be included in a third internal control group (group 3) not utilized in statistical comparison with the other two groups, but finalized to the evaluation of the case study’s appropriateness. In these patients, standard ALND will be performed. Patients enrolling in the study protocol will last 3 years. Patients should be studied for at least 5 years with clinical and instrumental follow-up periodic controls, prevised from actual standard guidelines. Endpoints: The primary endpoint of the study is the disease free survival rate (DFS) and will be evaluated from the entry date in the study to the date of the last contact, the date of the distant or locoregional relapse, or the date of death for any cause. Secondary endpoints are overall survival (OS), locoregional disease-free survival (LRDFS) and distant disease-free survival (DDFS) Citation Format: Corrado Tinterri, Emilia Marrazzo, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Alberto Testori, Valentina Errico, Giuseppe Canavese. Neonod Study: Conservation of axillary lymph nodes in the presence of micrometastases in the sentinel lymph node if cN- After neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-03.