RESUMO
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/µL). 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/µL 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/µL. CONCLUSIONS: In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/µL was associated with a higher progression risk and > 15,000 copies/µL was predictive of non-SLN involvement.
RESUMO
OBJECTIVE: To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). METHODS: This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. RESULTS: A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). CONCLUSIONS: TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST.