Discordance in pathology report after central pathology review in early breast cancer and its impact on treatment choice.

Abstract

585 Background: Systemic therapies in early breast cancer are chosen on the basis of predictive factors defined by immunohistochemistry. In large clinical trials the rate of discordance between local and central pathologic report is noteworthy. In this retrospective analysis we evaluated the discordance rate in histological report and the clinical impact on treatment decision, after central pathologic review of early breast cancer. Methods: A retrospective pathology review was performed on formalin-fixed and paraffin-embedded tissue from primary breast tumors collected from different Italian Cancer Centers from 2008 to 2010, by the Central Pathology Laboratory at the European Institute of Oncology in Milan. Central review included assessment of histologic subtype, grade, Ki-67, hormone receptors (ER/PgR) and HER2. HER2 status was also confirmed by FISH. Primary end-point was the discordance rate (DR) in ER, PgR, HER2 between local and central pathology. Results: 112 specimens from 10 cancer centers were reviewed. Ten locally ER positive (≥1 % ER and PgR) tumors were ER negative at the central review (DR 12.3 %). Ten ER negative tumors at the local evaluation changed in ER positive after central review (DR 32.3%). The overall DR for ER was 17.8% (95% CI, 10.7%-24.8%). Ten PgR positive tumors became PgR negative, 5 PgR negative tumors resulted PgR positive at central review (DR 14.3% and 12.2% respectively; overall DR 13.6% (95% CI, 7.2%-19.9%). Regarding HER2, 20 positive samples resulted negative (DR 54%), while 9 HER2 negative were positive at central report (DR: 13.3%) with an overall DR of 26.6% (95% CI, 18.1%-35%). These findings resulted in therapy change in 64 (57%) patients, mainly with avoidance of chemotherapy and trastuzumab prescription. Changes in percentage of ER and/or PgR from < 50% to > 50% immunoreactive cells or vice versa were found in 23 cases and resulted in different treatment choice (mainly exclusive endocrine therapy). Conclusions:In our retrospective analysis, the central pathologic review had a significant impact on the treatment choise in early breast cancers, as previously shown in clinical trials. Further studies are warranted in to confirm these provocative results.