Her-2/neu amplification and breast cancer survival: Results from the Shanghai breast cancer study

Abstract

Her-2/neu is a member of the epidermal growth factor receptor family that has been found to be overexpressed or amplified in ∼20-30% of breast cancers. Negative prognosticators and a shortened survival have been shown to be associated with these changes in Her-2/neu, but previous studies have consisted of predominantly Caucasian populations. Additionally, chromogenic in situ hybridization (CISH) has been suggested to be a potential alternative to fluorescent in situ hybridization (FISH), the expensive and labor-intensive gold standard assay currently used for Her-2/neu amplification. This study evaluated breast cancer samples from 313 Chinese women participating in the Shanghai breast cancer study, of which 100 (32%) were found to have Her-2/neu amplification by either FISH or CISH methodologies. After a mean follow-up period of 6.67 years, Her-2/neu amplification was found to be significantly associated with an increased hazard of death, regardless of which assay was used to detect amplification. Patients with Her-2/neu amplification were ∼60% more likely to die of the disease (HR: 1.6, 95% CI: 1.0-2.6) than patients without amplification, even after adjusting for age, stage, menopausal status, chemotherapy, radiotherapy and tamoxifen treatment. Furthermore, the negative prognostic effect of Her-2/neu varied by cancer stage, with greater risks of death evident among later stage patients. This study supports a negative prognostic role for Her-2/neu in breast cancer survival among a Chinese population, irrespective of whether FISH or CISH is used to detect amplification of the Her-2/neu gene.