The role of HER-2 in Breast Cancer.

Human epidermal growth factor receptor type2 (HER-2) was emerged as a molecular biomarker in breast cancer, as important as the estrogen-receptor (ER). It is located on chromosome 17q21.1 and is a member of the type I growth factor receptor family. In breast cancer, HER-2 is over-expressed in 20%–30% of primary tumors. The clinical behavior of human breast cancer associated with this gene was originally demonstrated in 1987 [1]. According to the initial report, HER-2 gene amplification could independently predict the time of disease relapse and overall survival in breast cancer patients. Thus, this gene is considered as one of the prognostic factors for breast cancer [2, 3]. However, conflicting results were reported later [4, 5]. This may be partly because of differences in the methodologies used to determine HER-2 status. At present, HER-2 is not considered a definite and independent prognostic marker of breast cancer [6]. Along with estrogen receptor (ER), HER-2 is an important gene for molecular targeting treatment of breast cancer. Thus, as a predictor of the efficiency of HER-2-targeted therapy, HER-2 status is established by a number of studies. Breast cancer cases with over expression of HER-2, as determined by immunohistochemistry or gene amplification by fluorescence in situ hybridization (FISH) showed a high rate of response to HER-2-targeted therapy [6]. For the treatment of breast cancer, HER-2 is useful from 2 clinical aspects as a target of HER2 inhibitors and a predictor of the efficiency of anti-cancer agents. Inhibition of HER-2 is necessary for treating breast cancer with HER-2 over expression (HER-2 subtype). At present, molecule-targeting drugs against HER-2, such as trastuzumab and lapatinib, are successfully used on a routine clinical basis, although the long-term outcome is still unknown. Without HER-2 Inhibitors, treatment would not be possible for cancers of the HER-2 subtype. HER-2 could also be used as a predictor of the efficiency of cytotoxic agents. ER negativity, proliferating markers, and HER-2 over expression can be used to predict the efficacy of any anti-cancer agent. Although there is no specific predictor for individual anti-cancer agents, HER-2 seems to be the most promising predictor, especially for anthracycline. Meta-analyses have revealed that the efficacy of anthracycline is confined to HER-2 subtype cancers [7-10]. Anthracycline is still a primary drug for the treatment of breast cancer, but from these findings, it seems that the use of anthracycline for the chemotherapy for breast cancer is questionable. For the treatment of HER-2 subtype breast cancers, a combination of anti-cancer agents and HER-2 inhibitors needs to be considered because HER-2 inhibitors are indispensible for this treatment. We need to determine whether anthracycline can be used as an anti-cancer agent in combination with HER-2 inhibitor. As the mechanisms of breast cancer development and proliferation are being elucidated, the strategies for treating breast cancer have also changed drastically. I intend to review and discuss the influence of HER-2 on individual treatment strategies for breast cancer.