Is it Possible to Predict Non Sentinel Node Positivity on the Basis of mRNA Copy Numbers of CK19 Receptor in Breast Cancer?

In operable breast cancer One step nucleic acid amplification (OSNA) provides intraoperative diagnosis of sentinel lymph nodes (SLN) by assaying the mRNA copy numbers of cytokeratin 19 (CK19) receptor. If the OSNA shows macromets patients go on to have axillary lymph node dissection (ALND). Several nomograms have been developed using m RNA copy numbers alone or in combination to predict in which patients the NSLN would be positive. In low risk patients ALDN can be avoided. Our study was designed to establish is there is any correlation between m RNA copy numbers and the likelihood of positive NSLN. Of the 1159 patients who had sentinel lymph node biopsy 120 underwent axillary lymph node dissection. Of the patients who had ALND 69 (57%) had positive NSLNs and 51 (43%) patients had negative non sentinel lymph nodes. The mean mRNA copy numbers respectively for the 2 groups are 609,855 and 853,665. The difference is not statistically significant. The area under curve for both the groups was similar establishing that m RNA copy numbers alone cannot be used as a discriminator in predicting the likelihood of positive NSLN. Aims: To determine if there is any correlation between the number of positive non-sentinel lymph nodes (NSLN) and the mRNA copy numbers of cytokeratin 19 receptor on one step nucleic acid amplification (OSNA) in the sentinel lymph node (SLN). Methods: An 8-year retrospective study of consecutive patients who had primary surgery and sentinel node biopsy for breast cancer from January 2011 to December 2018 was carried out. All these patients had intraoperative analysis of sentinel lymph nodes by OSNA. Patients who had neoadjuvant chemotherapy or neoadjuvant endocrine therapy were excluded. Results: There were 1159 patients with an age range of 24 to 90 years and a mean age of 63 years in this study. A total of 1324 SLNs were analyzed by OSNA. Macrometastasis was found in 120 patients and they underwent axillary lymph node dissection (ALND). A total of 2405 NSLNs were analyzed. Of the patients who had ALND, 51 (43%) patients had negative NSLNs and 69 (57%) had positive NSLNs. The mean mRNA copy numbers respectively for the 2 groups were 853,665 and 609,855. The difference between the means is not statistically significant (P = 0.82). Also the Receiver Operating Characteristic (ROC) Curve of the total CK-19 mRNA copy number for both groups-negative and positive NSLN were almost identical (Figure 3) indicating mRNA copy numbers cannot be used to discriminate between positive and negative non-sentinel lymph nodes. Conclusion: It is clear from our study that in patients who have ALND due to macromets on OSNA, there is no correlation between the total tumor load as represented by mRNA copy numbers and the likelihood of positive non-sentinel lymph nodes. We therefore cannot rely solely on the mRNA copy numbers to decide on ALND.