Study of CYP2C19 and ALDH3A1 Polymorphisms in Breast Cancer Patients

Breast Cancer Patients

Genetic polymorphisms of metabolic enzymes may influence the metabolism of Doxorubicin-Cyclophosphamide regimen in breast cancer patients. the investigators want to 1. evaluate the frequency or incidence of the genetic polymorphisms of CYP2C19 and ALDH3A1 in breast cancer patients, and 2. analyze the association between the genetic polymorphisms of CYP2C19 and ALDH3A1 and toxicities in breast cancer patients treated by Doxorubicin-Cyclophosphamide regimen therapy.

Breast cancer refers to the erratic growth and proliferation of cells that originate in the breast tissue, most commonly from the inner lining of milk ducts (ductal cancers) or the lobules that supply the ducts with milk (lobular cancers). Breast cancer is about 100 times more common in women than in men, although males tend to have poorer outcomes due to delays in diagnosis. Alteration in hormonal level and Family history of breast cancer are risk factors for breast cancer. The classic symptom for breast cancer is a lump found in the breast or armpit. Doing monthly breast self-exam (BSE) is a great way to be familiar with the breasts' texture, cyclical changes, size, and skin condition. Breast cancer is usually diagnosed by biopsy of nodule detected by mammogram or by palpitation. Today there are so many approaches, which can be made for the treatment of breast cancer such as surgery, radiation therapy, chemotherapy, hormonal therapy and recently nanotechnology and gene therapy. Chemotherapy is the use of anti-cancer drugs to treat cancerous cells. The differences in patients' response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. Four cycles of doxorubicin and cyclophosphamide (AC) chemotherapy regimen has become a standard regimen. No chemotherapy regimen administered for four cycles has proven to be superior to AC. The undeniable advantage of this therapy scheme is low cost of treatment, its proven efficacy and mostly acceptable toxicity. Hematological (neutropenia and anemia) and gastrointestinal (nausea, vomiting and mucositis) toxicities are common in patients treated with AC regimen. Doxorubicin is metabolized by the CBR (carbonyl reductase) enzymes to its active component. Similarly cyclophosphamide, the cell cycle nonspecific prodrug, requires activation by a number of different cytochrome P450 enzymes, mainly of CYP2C family. The transport systems are also crucial for the treatment outcome, as both importers and exporters are responsible for the cellular drugs' concentration. It is expected that any variation that affects metabolic enzymes and transporter activity would be reflected in not only the response to treatment, but also in the development of drug-related toxicity. Each of these enzymes and transporter genes is known to exhibit a degree of genetic variation, characterized by single nucleotide polymorphisms (SNPs). In particular, there have been few investigations of the possible influence of variations in the genes encoding transporters and drug metabolizing enzymes relevant for the two drugs. Pharmacogenomic analysis offers the promise that personalized regimens may be identified for individuals who might have more favorable outcomes with certain chemotherapies. Specifically, because genetic variation in metabolic enzymes is one determinant of drug concentration, pharmacogenomics has been proposed as an approach to tailor drug choice or dose to optimize efficacy and reduce toxicity of cancer treatments.

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