Breast cancer is a common squamous cell carcinoma. China’s women’s cancer patients, the number of breast cancer ranked second; Globally, breast cancer, women’s second cause of death. The author at home and abroad literature on trastuzumab targeted therapy of breast cancer provide a comprehensive overview of progress.
Currently known human epidermal growth factor receptor -2 (HER-2) is now a clearer understanding of human cancer and breast cancer closely related to genes, it is highly expressed in breast cancer often precedes estrogen receptor (ER) negative, tend to have lymph node metastasis and poorly differentiated tumors, the prognosis is poor. With in-depth study of HER-2, it has become one of the breast cancer-specific molecular target therapy.
Has been FDA approved trastuzumab is a recombinant DNA human monoclonal antibodies from mammalian cells (Chinese large voles eggs) in the nutrient solution containing gentamicin suspension culture made of. Selective effects of trastuzumab on HER-2, with a high degree of affinity, with a high degree of targeting, only works on cancer cells, while normal cells of anti-small, is a contemporary representation of targeted therapy of breast cancer drug .
Basic research shows that about 25% to 30% of breast cancers are HER-2 genetic changes to promote increased HER-2 tumor cells. Trastuzumab selectively with a solid combination of HER-2, inhibit proliferation of cancer cells for HER-2 over-expression in breast cancer patients.
Studies have shown that trastuzumab treatment of breast cancer is mainly through the mechanism of HER-2 receptor-specific binding, affecting the growth of the signal transmission; for HER-2 receptor protein internalization degradation; by ADDC role of the immune aggregation cells to attack and kill tumor cells; In addition, it can be reduced vascular endothelial growth factor and other vascular growth factor activity. Positive HER-2 status is trastuzumab therapy is absolutely essential, therefore, a correct evaluation of HER-2 status is crucial. There are two commonly used detection methods: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The former detection of HER-2 protein expression level, which is on HER-2 gene amplification for qualitative analysis. Clinical trial has been fully demonstrated IHC (3 +) or FISH (+) from drug treatment in patients with the greatest gains.
Abroad, two key clinical trials (H0649g and H0648g) and trastuzumab monotherapy as first-line therapy in clinical trials (H0650g) have shown that the earlier the application of the drug, patients benefit from the greater. Vitro and in vivo studies indicate that this product combined a variety of chemotherapy drugs also have synergistic effects, or superimposed. Two large-scale clinical trials also showed that, for some patients with metastatic breast cancer alone, the FDA may be a more reasonable choice. The FDA alone does not reduce the early stage after it is combined with other chemotherapy drugs effects. Another study showed, compared with chemotherapy alone, the drug combined with chemotherapy drugs can increase the high expression of HER-2 treatment of patients with metastatic breast cancer is efficient, to extend the recurrence time, also extended the survival time of patients.
Trastuzumab combined first-line treatment of docetaxel and HER-2 (+) metastatic breast cancer patients can significantly prolong the survival period, which is French scholar MichelMarty at the 12th Annual European Clinical Oncology (ECCO) posted on the M77001 â…¡ of Results.
The study results showed that single-agent group total effective rate was 36%, while the combined treatment group the total effective rate as high as 61%, this difference was significant statistical significance (p = 0.001); single-agent group median response duration 4.2 months, the combination group was 8.3 months; two groups, the median progression-free survival period of the disease are also significant differences: single-agent group 6.1 months, combination therapy group was 10.6 months (p = 0.0001). The study also showed that combination therapy group, median survival (27.7 months) longer than the monotherapy group (18.3 months), but even after failure of monotherapy with trastuzumab can still get satisfactory results, with a median survival time may be extended to 21.9 months, but could not achieve the treatment is started on trastuzumab combined with the results obtained.
In the end, the researchers reached the following conclusions: Trastuzumab combined docetaxel as HER-2 (+) metastatic breast cancer in first-line treatment programs more effective than single-agent docetaxel chemotherapy, and are well tolerated.
