Abstract PD06-04: Relevant Impact of Central Pathology Review on Nodal Classification, but Not on the Association of Small Nodal Metastases with Breast Cancer Outcome. Results from the Dutch MIRROR Study
Authors: Vestjens JH , de Boer M , Borm GF , van Deurzen CH , van Diest PJ , van Dijck JA , Adang EM , Nortier JW , Rutgers EJ , Seynaeve C , Menke-Pluymers MB , Bult P , Tjan-Heijnen VC. 
Published: April 2011

Abstract
Background: Previously, we reported that isolated tumor cells, pN0(i+), or micrometastases, pN1mi, were associated with a reduced 5-year disease-free survival (DFS) rate among patients with favorable early-stage breast cancer who did not receive adjuvant systemic therapy (AST) (de Boer et al, NEJM 2009). In patients with pN0(i+) or pN1mi who received AST, DFS was improved. Patients were classified by N-status as determined after central pathology review and restaged according to the 6th AJCC classification. In real life, however, treatment decisions are based on the pathology reports performed by local pathologists. Therefore, in the present study we addressed the role of the central pathology review. Methods: In the MIRROR study, a total of 2707 patients were included. Involved women were operated for breast cancer in a(ny) Dutch hospital in 1998-2005, had favorable characteristics (tumor size 1-3 cm and differentiation grade I-II OR tumor size 1 cm irrespective of grade) and had undergone a sentinel node procedure with pN0(i+) or pN1(mi) as final N-status. A control group with low-risk node-negative disease was randomly selected from the years 2000 and 2001. We assessed the difference between the original N-status and N-status after central review. Further, in patients who had not received AST (n=1712), 5-year DFS was assessed according to the original N-status as well as the review N-status. Results: Of 856 patients with pN0 after central review, 0.4% patients were originally staged as pN0(i+). Of 819 patients with reviewed pN0(i+), 24% patients originally had pN0 and 20% patients pN1 mi. And, of 1032 patients with pN1mi after review, 3% patients had originally pN0 and 15% patients pN0(i+). Overall, central review changed the N-classification thereby in 20% of patients. In patients who did not receive AST, the 5-year DFS rates of cohorts based on central pathology review were 86% for pN0, 77% for pN0(i+) and 76% for pN1mi (P&lt;0.001, pN0(i+) and pN1mi compared with pN0). According to the original staging, the 5-years DFS rates were 85% for pN0, 73% for pN0(i+) and 72% for pN1mi (P&lt;0.001; pN0(i+) and pN1mi compared with pN0).
Conclusion: Central pathology review changed the N-classification in 20% of patients. On a population level the association of isolated tumor cells and micrometastases with breast cancer outcome remained unchanged. However, on an individual patient level, the upstaging of pN0 patients may be of clinical relevance. Quality control of pathology departments should therefore also include nodal staging of breast (and perhaps other) cancers.
Support: The Netherlands organization for health research and development (ZonMw) and the Dutch Breast Cancer TrialistsGroup (BOOG)
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-04.