Validation of prognostic and predictive value of total tumoral load after primary systemic therapy in breast cancer using OSNA assay

Purpose This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study.Methods/patients This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250-25,000, and > 25,000 copies/mu L). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves.Results We included 263 patients with a mean age of 51.4 (+/- SD 10.5) years. Patients with TTL > 25,000 copies/mu L had a shorter DFS (HR 3.561 [95% CI 1.693-7.489], p = 0.0008 vs. TTL <= 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/mu L.Conclusions In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/mu L was associated with a higher progression risk and > 15,000 copies/mu L was predictive of non-SLN involvement.