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Introduction


Breast cancer is the most frequently diagnosed cancer globally and is the leading cause of cancer-related death in women, with about 1.4 million women worldwide diagnosed with breast cancer every year and five hundred thousand women die of breast cancer. The incidence of breast cancer in China increased year by year, seriously endangering women's health and life,  Although the diagnosis of breast cancer and treatment methods continue to improve.

Breast cancer is highly heterogeneous. According to the difference in gene expression profile, the molecular classification of breast cancer is roughly divided into four types, including Luminal type A, Luminal B type, HER-2 positive and triple negative breast cancer (TNBC), each type of breast cancer can be divided into different types according to the different carcinogenic genes, then the physicians  select corresponding chemotherapy drugs or targeted drugs according to the specific mutation.


Targeted drugs screening

Both BRCA genes are tumor suppressor genes that produce proteins that are used by the cell in an enzymatic pathway that makes very precise, perfectly matched repairs to DNA molecules that have double-stranded breaks. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Women with harmful mutations in either BRCA1 or BRCA2 have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal. The cancer risk caused by BRCA1 and BRCA2 mutations are inherited in a dominant fashion even though usually only one mutated allele is directly inherited. This is because people with the mutation are likely to acquire a second mutation, leading to dominant expression of the cancer.

Human epidermal growth factor-2 (HER-2) is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. Amplification, also known as the over-expression of the ERBB2 gene, occurs in approximately 15-30% of breast cancers. It is strongly associated with increased disease recurrence and a poor prognosis. HER2 is the target of the monoclonal antibody trastuzumab (marketed as Herceptin). Trastuzumab is effective only in cancers where HER2 is over-expressed. One year of trastuzumab therapy is recommended for all patients with HER2-positive breast cancer who are also receiving chemotherapy. An important downstream effect of trastuzumab binding to HER2 is an increase in p27, a protein that halts cell proliferation. Another monoclonal antibody, Pertuzumab, which inhibits dimerisation of HER2 and HER3 receptors, was approved by the FDA for use in combination with trastuzumab in June 2012. HER2 testing is performed in breast cancer patients to assess prognosis and to determine suitability for trastuzumab therapy. It is important that trastuzumab is restricted to HER2-positive individuals as it is expensive and has been associated with cardiac toxicity. For HER2-negative tumours, the risks of trastuzumab clearly outweigh the benefits.


Evaluation of the efficacy and side effects of chemotherapy drugs

The development of pharmacogenomics theory and technology has provided us with more information.  Genetics may account for much of the variability in the patients responses to drug therapies. Polymorphisms that affect the pharmacokinetics and

pharmacodynamics of specific drugs are common. Testing for certain polymorphisms before prescribing certain drugs could help avoid adverse drug effects and improve efficacy. Pharmacogenomic testing has only recently begun to enter clinical practice, and routine testing is currently limited to a few clinical scenarios. However, additional applications may be just around the corner.


Reference

1.China Anti-Cancer Association Breast Cancer Professional Committee. Expert consultation on clinical diagnosis and treatment of advanced breast cancer in China (2016 edition). Natl Med J China,2016,96(22):1719-1727.
2.China Anti-Cancer Association Breast Cancer Professional Committee. Chinese Cancer Society Guidelines for Breast Cancer Diagnosis and Treatment (2015 edition. China Oncology,2015,25(9):692-754.
3.Zhang Juan, Sun Jie, Ouyang Tao, et al. Relationship between Clinical Pathological Features and Chemotherapeutic Outcomes in Women with BRCA1 and BRCA2 Mutation- Negetive Familial Breast Cancer. China J Oncol,2016,38(3):185-189.
4.NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. 2016.V2
5.NCCN Clinical Practice Guidelines in Oncology. Genetic/ Familial High-Risk Assessment: Breast and Ovarian. 2017. V2.