37P HER2 Tumor Heterogeneity and Discrepancies in HER2 Status Between Primary Tumor and Corresponding Circulating Tumor Cells in Metastatic Breast Cancer Patients

Abstract

ABSTRACT Introduction Presence of circulating tumor cells (CTCs) in peripheral blood of patients with metastatic breast cancer (MBC) represents an independent prognostic factor. Discrepancies in HER2 status between primary breast tumors and CTCs have been reported. Indeed, 5-38% of patients with HER2 negative (HER2-) primary breast cancers show HER2 overexpression in corresponding CTCs at time of metastatic disease. However, the biological explanation of such discrepancies is still matter of debate. Sparse reports indicate that 5-30% of breast cancers show HER2 heterogeneity. We hypothesize that heterogeneity of HER2 expression within HER2- primary tumors might explain the presence of HER2 positive (HER2+) CTCs. Methods We analyzed 14 CTC positive (≥ 2 CTCs/7.5ml blood) MBC patients whose primary tumors were HER2- according to the adjuvant trastuzumab trials criteria. CTCs were evaluated for HER2 expression by immunofluorescence (CellSearch™ System, Veridex LLC) and defined positive if ≥ 50% cells stained for HER2. According to these criteria, seven of the patients had discordant HER2+ CTCs (cases), while seven had concordant HER2- CTCs (controls). For both cases and controls, we evaluated HER2 status by immunohistochemistry on additional tumor-bearing blocks, either from the primary tumor or from synchronous metastatic axillary lymphnodes (average of 3 blocks/patient). HER2 heterogeneity was defined as presence of incomplete or complete membrane staining in Results Five of the seven (71%) discordant cases showed HER2 heterogeneity. Heterogeneity was present either in the additional primary tumor blocks (40%) or in the metastatic axillary lymphnodes (40%) or in both (20%). Intriguingly, none of the concordant cases (controls) showed HER2 heterogeneity. Conclusion Here we show that areas of HER2 expression in HER2- tumors are associated with the presence of HER2+ CTCs at time of metastatic disease, suggesting that HER2+ clones might be selected during cancer progression. Trials investigating whether patients with HER2 heterogeneous tumors might benefit from HER2 targeted therapies are warranted. Disclosure A. Di Leo: Dr. Di Leo received research grants from GSK and honoraria as a speaker at satellite symposia or as a consultant from Roche and GSK. All other authors have declared no conflicts of interest.