HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

This retrospective study investigates the correlation of intra-individual HER2 status between primary breast cancers and corresponding recurrences in a population derived cohort. The REMARK criteria were used as reference. In 151 breast cancer patients, primary tumors were analyzed for HER2 status on histopathology sections using immunohistochemistry (IHC) confirmed by fluorescence in situ hybridization (FISH) for IHC 2+ and 3+. Recurrences (loco regional and distant) were investigated by aspiration cytology, using HER2 immunocytochemistry (ICC) or FISH (ICC in 84 patients and FISH in 102 patients). In the 151 patients, sites of recurrence were bone/bone marrow 30%, liver 16%, local recurrence 18%, lung/pleura 10%, axillary lymph nodes 9%, skin (non-local) 7%, supra clavicular lymph nodes 5%, and other sites 7%. In 15 patients (10%) HER2 status changed, 7 of 108 patients (6%) from HER2 negative to HER2 positive and 8 of 43 (19%) from HER2 positive to HER2 negative. Intra-patient agreement in HER2 status was 76% (95% CI 64-87%), and the disagreement was 10% (95% CI 5-15%). The multivariable Cox analysis showed a significantly increased risk of dying in the patient group with changed HER2 status compared to patients with concordant positive HER2 status. Overall survival HR is 5.47 (95% CI 2.01-14.91) and survival from relapse HR is 3.22 (95% CI 1.18-8.77). The unstable status for HER2 in breast cancer is clinically significant and should motivate more frequent testing of recurrences.