HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

Abstract

Summary:We retrospectively evaluated the predictive and prognostic role of HER2 expression in 44 metastatic breast cancer (MBC) patients treated with high-dose consolidation chemotherapy (HDCT) and autologous stem cell support after induction chemotherapy (IC) with six courses of epirubicin þ paclitaxel (22 patients) or gemcitabine þ epirubicin þ paclitaxel (22 patients). HER2 expression was evaluated by an immunohistochemical method (Herceptest, Dako). A total of 13 patients (29.5%) showed a HER2 overexpression (score 3 þ ). After IC, nine patients were in complete response (CR), 30 in partial response (PR), and five in stable disease (SD); after HDCT, 20 (45.5%) obtained a CR, and 23 were in PR, for a conversion rate of 48.5%. Conversion rate for HER2-positive patients was 87.5 vs 37% for HER2-negative patients (P ¼ 0.018). The median progressionfree (PFS) and overall survivals (OS) were 17.6 (95% CI 13.2-22.0) and 44 (95% CI 25.9-62.3) months, respectively. Patients with HER2 overexpression experienced a significantly (P ¼ 0.0042) shorter median PFS (15.3 months, 95% CI 11.1-19.5) compared to HER2-negative patients (21.3 months,). The median OS was 27.6 months (95% CI 4.5-50.7) in HER2-positive patients and 50.3 months (95% CI 38.7-62.0) in HER2-negative patients (P ¼ 0.345). These results indicate that HER2 overexpression predicts a worse outcome for patients with MBC treated with HDCT, despite the high CR rate obtained in this subset of patients.

Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells

“…Amplification of HER2/ neu and the resulting overexpression of its encoded neu proteintyrosine kinase p185neu may transform cells by chronically stimulating the signal transduction pathway (Di Fiore et al, 1987). Overexpression of HER2/neu has also been shown to correlate with tumor grade, tumour size, lymph node metastasis, survival and resistance to hormonal therapy and chemotherapy in breast cancer patients (Korkolis et al, 2004;Fehm et al, 2004;Guarneri et al, 2004). An intact kinase domain is essential for activation of numerous downstream effectors, including phospholipase Cγ, PI3K/AKT and ERK1/2, which result in DNA synthesis and cell proliferation (Bohn et al, 2002;Alimandi et al, 1997;Montgomery et al, 2005;Price et al, 1999).…”

Remote Optical Switch for Localized and Selective Control of Gene Interference

“…After validating steps essential in using ONCOS, we carried out ONCOS in breast carcinoma cells to block the mRNA translation of ERBB2, an oncoprotein commonly overexpressed in 20–30% of breast cancers 40. General transfection methods of bringing DNA into cells, such as viral vectors or cationic liposome-mediated transfection, lack the spatial and temporal control of gene interference.…”

Complete Response after High-Dose Chemotherapy and Autologous Hemopoietic Stem Cell Transplatation in Metastatic Breast Cancer Results in Survival Benefit

“…In patients with oligo‐metastatic breast cancer, aggressive local treatment including local surgery or radiation, followed by PSCT has shown promising RFS (9). Patients with HER‐2 neu overexpressing breast cancer had worse outcome after HDC, compared to HER‐2 neu negative tumors (10–12). The presence of occult tumor cells contaminating the peripheral blood apheresis product has shown to adversely affect event‐free survival, but not OS (13).…”