Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients

Objective To assess the intraoperative positive sentinel lymph node (SLN) total tumor load (TTL, defined as the amount of CK19 mRNA copies [copies/μL] in all positive SLNs) obtained by one-step nucleic acid amplification (OSNA) and to determine whether it is predictive of non-SLNs involvement. Summary background data The OSNA assay (Sysmex Corporation, Kobe, Japan) is a new diagnostic technique that uses molecular biological techniques to analyze SLN that has been validated as an accurate method for detection of positive SLN. Although the American College of Surgeons Oncology Group Z0011 trial has defined a select cohort of patients in whom a completion axillary lymph node dissection (cALND) may be safely omitted, there are a still a number of patients where prediction of non-SLN metastasis may be helpful for cALND decision making. Multiple studies suggest that specific pathologic characteristics of the primary tumor and the SLN metastases are associated with an increased likelihood of additional positive non-SLN. Methods This is a retrospective multicentric cohort study of 697 patients with cT1-3N0 breast cancer, who had had intraoperative SLN evaluation by OSNA assay with a cALND. TTL is defined as the amount of CK19 mRNA copies number in all positives SLN (copies/μL). Results Univariate logistic regression showed that, in addition to TTL (p < 0.001), the number of affected SLNs (p < 0.001), tumor size (p < 0.001), HER2 status (p = 0.007), and lymphovascular invasion (LVI, p < 0.001) were predictive of ALND status. The multivariate logistic regression analysis showed that TTL is an independent predictor of metastatic non-SLNs, after adjusting for the tumor size, HER2 status, LVI and, in particular, the number of affected SLNs. Conclusions TTL by OSNA is a newly standardized and automated tool that predicts axillary node status better and independently of the number of affected SLNs and the type of surgery. This value can then help clinicians to personalize surgical treatment. Prospective studies will be carried out to determine the clinical impact of this variable in the management of patients.