Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer

Abstract

Keywords:Breast cancer One-step nucleic acid amplification Sentinel lymph node Non-sentinel lymph node metastasis Axillary lymph node dissection Total tumor load a b s t r a c t Background: This study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and nonsentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability. Methods: We conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria. Results: In the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06e6.70; P ¼ 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69e0.92) was achieved. For TTL >1.9 Â 10 5 copies/mL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases. Conclusion: When using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection.

Intraoperative Nomograms, Based on One-Step Nucleic Acid Amplification, for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis

“…Peg et al first reported the concept of TTL, defined as the amount of CK19 mRNA copies in all positive SLNs, 25 and concluded that TTL was an independent predictor of NSLN metastasis by using multivariate analysis of tumor size, human epidermal growth factor receptor 2 (HER2), LVI, and the number of metastatic SLNs. The result was consistent with that reported by Nabais et al 27 TTL comprises two elements (the number and the size of SLN metastases), indicating that TTL can accurately estimate axillary tumor burden as one continuous variable. Moreover, the advantage of TTL as a predictive parameter is that TTL is automatized, reproducible, and can be assessed intraoperatively.…”

Analysis of factors related to non-sentinel lymph node metastasis in 296 sentinel lymph node-positive Chinese breast cancer patients

“…Therefore, non-NSLN involvement could not be accurately evaluated in these patients. Second, the influence of total tumor burden and pathological tumor stage were not investigated, although these have been previously identified as useful predictors of non-NSLN metastasis 35-36 . …”

One‐step nucleic acid amplification CK19 copy number for sentinel node biopsy in breast cancer: Identification of new cutoffs to predict nonsentinel axillary node involvement

“…The aforementioned studies include both micro‐ and macrometastatic cases as many predate the acceptance that micrometastatic disease does not warrant automatic ALND. Reviewing the literature, two studies have reported cutoffs for macrometastatic disease: Nabais 16 studied 58 patients with a TTL cutoff of 190 000 copies/µL (73.3% sensitivity; 74.4% specificity), and Fung 8 studied 122 patients and used a cutoff of 15 000 (sensitivity 0.815; specificity 0.908) to discriminate between >2 and <2 involved nodes in line with Z0011 practice. Future research should focus on macrometastatic disease given the aforementioned change in international practice.…”