Association of basal marker expression with outcome and trastuzumab resistance in HER2-positive breast cancer.

Abstract

608 Background: Herceptin resistance is a significant challenge in the treatment of Her2-positive (Her2+) breast cancer. A subset of Her2+ breast cancers are known to express basal genes (basal Her2). We investigated the effect of basal gene expression on cell viability and Herceptin response in Her2+ breast cancer cell lines and on prognosis in patients with Her2+ breast cancer who received Herceptin. Methods: We selected 4 cell lines to represent basal Her2 (HCC1569, HCC1954) and non-basal Her2 (BT474, SKBR3) breast cancer based on their basal gene signature in microarray analysis, and treated each with vehicle, Herceptin (H), Paclitaxel (P), and H + P. Cell viability was assessed by MTT assays. Her2 pathway suppression was compared between groups using immunoblotting with anti-Her2, p-AKT, p-ERK antibodies. Expression of CK5/6, CK14, and EGFR was evaluated after immunohistochemical staining in paraffin-embedded tissue of 88 patients with Stage 1-3 Her2+ breast cancer treated with chemotherapy and Herce...