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Abstract
Hereditary predisposition to breast and ovarian cancer and responsible for autosomal-dominant transmission, most commonly due to germline mutations in BRCA1 and BRCA2 has been recognized for many years. Hereditary breast cancer is characterized by early age at onset, bilaterality, vertical transmission through both maternal and paternal lines, and familial association with tumors of other organs, particularly the ovary and prostate gland. Most of the BRCA1 and BRCA2 mutations are predicted to produce a truncated protein product, supporting the hypothesis that they are tumor suppressor genes. Progress in determining the function of BRCA1 and BRCA2 suggests that they are involved in two fundamental cellular processes, DNA damage repair and transcriptional regulation.
Several series have examined the prevalence of germline BRCA mutations in population or hospital based samples of breast cancer patients mainly European ancestry and studies have demonstrated BRCA1/2 mutation between 5% and 10% with early-onset breast cancer. The assessments of familial cancer risk are extremely varied, including families from different ethnic backgrounds with greater or less numbers of affective relatives at varying ages. And estimates of penetrance for BRCA1 and BRCA2 mutations range from 36% to 85% for breast cancer, and 16% to 60% for ovarian cancer.
For molecular correlations, BRCA1 cancers were shown to be more often estrogen receptor negative, more high grade tumors and more frequent mutations in p53 than nonhereditary cancers. The phenotype for BRCA2-related tumor sappears to be more heterogeneous. The prognosis of BRCA related tumor is elusive, despite of a significantly increased risk of contralateral breast cancer.
Surveillance recommendations for women with germline BRCA mutations are necessary and women are encouraged to learn and practice breast self-examination beginning at age 18 and to begin annual mammogram screening at age 25. A number of women with BRCA mutations may consider undergoing surgical procedures (mastectomy and salpingooophorectomy) in attempt to reduce their risk. Nonsurgical options (tamoxifen medication) for the prevention of hereditary breast cancer are currently limited.
The choice of whether to undergo genetic testing is difficult one and should be made only after extensive consultation with a professional who is well versed in the counselling and management of families at hereditary risk. And psychological consequences of testing and the potential impact on family dynamics are important considerations that must be individually addressed.
Most of above mentioned data are based on studies of European ancestry. To apply these results to Korean patients with breast cancer, we have to collect a lot of data specific to Korean patients. Therefore, it is needed to study many aspects of Korean breast cancer including age specific mutation prevalence, penetrance, molecular correlation, pathology, prognosis, surveillance and prevention options for women with BRCA mutations.
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