الفهرس 
EPIDEMIOLOGYOnly 14 pages are availabe for public view
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Abstract
Breast cancer (BC) is the most common malignancy in women, accounting for 31% of all female cancers, and responsible for 15% of cancer deaths in women. One million females worldwide are diagnosed with BC every year. Treatment of advanced BC is futile and disfiguring, making early detection have a high priority in medical management of the disease.
The risk factors of BC include genetic, environmental and hormonal. genetic risk factors contribute to about 5%-10% of all cases, 90%-95% of them result from somatic mutation and about 5%-10% are inherited as the result of germ line mutation in autosomal dominant BC susceptibility genes. Many genes have been found to increase susceptibility to cancer and are also associated with familial breast cancer.
These genes include Breast Cancer Anti-estrogen resistance-1 (BRCA1), Breast Cancer Anti-estrogen resistance- 2 (BRCA2), Ataxia Telangiectasia mutant gene (ATM), Phosphate and Tensin homology (PTEN) and Tumor Protein (P53). Several other less frequently predisposing genes are also involved but to lesser extent.
Germline mutations in either of the two predisposing genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast cancer. Women with either BRCA mutation have a cumulative lifetime risk of invasive breast cancer of about 55-85%. Generally, it has not been possible for clinician to determine which individual in a high risk families are carriers of BRCA mutations.
There are several models for assessing a women’s risk of having breast cancer, the most widely used is the Gail model. Identifying women at risk is very important so as to present for them the appropriate method of screening and counsel them about the risk reduction method suitable for them.
Efforts are underway to reduce the high incidence and mortality associated with breast cancer, which can be achieved by the early detection of women at high risk. Since genetic predisposition is the strongest risk factor, molecular testing can be considered as the only way for early detection of breast cancer. DNA testing for breast cancer susceptibility became an option after the identification of the BRCA1 and BRCA2 genes.
Analysis of BRCA1 and BRCA2genes makes it possible to identify predisposing mutations in affected persons and determine risks for family members. Once a mutation is identified in affected person, asymptomatic family members can be tested for this only mutation, since first degree relatives of patients with breast cancer have increased risk for early onset of this cancer.
Women, who may not have these mutations, may have undergone unnecessary intervention including prophylactic surgery. So the availability of the BRCA analysis has beneficial impact on the care and counselling of women at risk.
Breast cancer screening has proved to be effective in reducing breast cancer mortality. The mammography is the gold standard method for screening. Breast self-examination is no longer recommended but, breast awareness is encouraged instead, so as the women be familiar with their breast and notice any changes early.
Major organizations vary in their recommendations for clinical breast examination.variation is by age at initiation, breast cancer risk status, frequency of CBE performance, and the strength of language used to recommend CBE. WHO didn’t recommend for it, on the other hand it’s recommended annually by ASCO and NCCN.
Breast cancer can potentially be prevented in women consider at high risk for breast cancer. Life style modification like maintaining healthy body weight, being physically active and avoiding alcohol are simple way to reduce breast cancer and are recommended for all women at all risk levels.
Bilateral prophylactic mastectomy reduce the risk of breast cancer up to 95%.it has special indication.
Bilateral slaingo-oophercetomy had decrease BC risk and Ovarian cancer risk but it showed an increase in all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer, so BSO is an option for BRCA mutation carrier only in whom the potential benefit of the procedure are increased because of reduction in breast cancer by 50% also of ovarian cancer.
Tamoxifen is recommended selective estrogens receptor modulator (SERM) used as chemoprevention, several trials were done, and they proved effectiveness in breast cancer risk reduction.
Treatment of advanced breast cancer is often useless and disfiguring, making early detection is of high priority in medical management of the disease. Molecular testing is the only way for early detection of breast cancer. Mutational analysis for a limited set of founder mutations requires much less time, resources, and lab than complete sequencing. Recommendations can be made for public health action on molecular genetic testing.
The increased public awareness of the nature and prevalence of breast cancer may result in an increased demand for genetic testing for breast cancer susceptibility. It is valuable to offer genetic testing to newly diagnosed cases with breast cancer for the purpose of clinical management and as a mean to identify presymptomatic carrier relatives for prevention.
New treatments for certain types of genetic breast cancer (BRCA1) and (BRCA2) mutation causes; follows a new approach to the eradication of cancer cells by blocking an enzyme (PARP) where they can slow the growth of tumors resulting from the defect in the gene (BRCA2) in contrast to chemotherapy which kill both healthy cells and cancer. Perhaps PARP inhibitors will become a preventative treatment for high-risk women and would make prophylactic mastectomies obsolete.