上個月是世界乳癌月，因為有乳癌基因BRCA1與BRCA2的突變（統稱BRCA) 而做預防性乳房切除的議題再次被討論。女性大眾一生中約有八分之一的機率會得到乳癌，如果不幸有 BRCA 基因突變的女性則約有 80% 的機率會得乳癌 。（40% 的機率得卵巢癌）
很顯然有這個基因突變會大幅增加得到乳癌的機率。再者，有突變病人的乳癌比其他人更難治療也更容易復發。影星安潔莉娜∙裘莉就是因爲有這個基因的突變而決定做預防性的全乳房與卵巢切除。但為什麼各國的婦產科醫學會大都不推薦所有女性做BRCA 突變的檢測？ 早點知道基因檢測的結果會有壞處嗎？我自己尋找資料後希望與各位分享我的想法，希望大家能更了解這個題目。
基因是人體細胞內含的遺傳資訊單位，它像是身體裡的零件製造代碼，代碼寫錯時做出來的零件就會有問題，而代碼的儲存媒介是雙股DNA，它像拉鏈一樣接合以便保存遺傳資訊，待基因需要表現時細胞會把DNA像拉鏈一樣拉開，轉錄為mRNA 最終轉譯為蛋白質，而各種不同的蛋白質表現成了各種細胞的變化，形成外在人與人之間不同的表現 如酒渦或髮線。（可惜的是我兩者都沒有）顯性的基因變化代表只要從父母任一方遺傳到這個變化便會表現出來，隱性的基因變化代表必需從父母雙方都遺傳到這個變化才會表現出來。BRCA 屬於顯性基因。
健康BRCA基因製造的蛋白質可以抑制細胞不正常的增生而突變的結果，造成所製造的蛋白質無法有效的抑制細胞增生進而產生癌症，約400個人就有一個帶有此突變，對個人來說，只要花幾千塊可以找到這個高度致癌因子是否存在有何不可？在美國婦產科學會的調查中，只有40% 的醫生認為每位女性都可以做 ，我認為原因在於檢測結果的後續行動，在目前的科技下還沒有專家們明確的共識。 雖然有些方法可以降低BRCA突變病人發生乳癌的風險（如吃藥或手術）姑且不論這些方法本身含有的風險，但陽性不代表一定會得乳癌，而陰性也不代表得乳癌的機率會大幅降低。 (約90% 的乳癌病人都沒有BRCA突變) 所以尤其是對於無其他風險的健康女性來說 ，檢測結果背後意義，其複雜度與心理負擔遠比一般的抽血(如膽固醇檢測) 來的大許多，而其必要性也可受討論。
目前國際上的共識是除了需要詳盡的檢測前基因諮詢外，也建議已經有其他危險因子，如家族史 年齡早發(50歲前)乳癌，同患乳癌與卵巢癌的病人考慮做基因檢測，才會有比較大的幫忙。希望這些想法能幫助考慮做乳癌基因檢測的各位做參考，有不詳盡的方面也請多包涵。
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The breast cancer genes BRCA1 and 2 (BRCA) made its biggest fame with Angelina Jolie’s decision to undergo preventive breast and ovary surgical removal after learning she carries a pathogenic mutation of BRCA. There is about a 1 in 8 chance of getting breast cancer in a woman’s lifetime. With the BRCA mutations, the risk of developing breast cancer can be as high as 80%. (and about 40% chance of developing ovarian cancer).
Having a pathogenic mutation in BRCA greatly increases the risk of developing breast cancer (and ovarian cancer). Moreover, breast cancer in patients with BRCA mutation tends to be more aggressive and more likely to recur. It seems intuitive to screen for BRCA mutation in every woman. However, most professional bodies around the world do not recommend routine BRCA testing because the carrier rate is low (approximately 0.25% in the general population). Also, there is no conclusive evidence on non-surgical methods of risk reduction. (Hormone antagonists such as Tamoxifen has only been shown to reduce breast cancer in the general population but not patients with BRCA mutation)
Prophylactic mastectomy and oophorectomy is very effective at reducing the risk of breast ( 50% reduction) and ovarian cancer (80% reduction) in patients with BRCA mutation, although the risk is not completely eliminated. However, not everyone who carries the BRCA gene will develop breast/ovarian cancer, so there is potentially an unnecessary surgical risk if one chooses to undertake prophylactic surgery.
Pre-test genetic counselling should be considered in everyone who wishes to take the BRCA testing. Currently the recommendation for women is those who have a strong family history of breast cancer, breast cancer younger than 50 years of age or patients with both breast and ovarian cancer.
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BRCA: The Breast Cancer Gene [Internet]. National Breast Cancer Foundation. [cited 2020 Nov 29]. Available from: https://www.nationalbreastcancer.org/what-is-brca/
Kim E-K, Park SY, Kim S-W. Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients. J Pathol Transl Med. 2020 May 14;54(4):265–75.
Hung F-H, Wang YA, Jian J-W, Peng H-P, Hsieh L-L, Hung C-F, et al. Evaluating BRCA mutation risk predictive models in a Chinese cohort in Taiwan. Scientific Reports. 2019 Jul 15;9(1):10229.
Sung P-L, Wen K-C, Chen Y-J, Chao T-C, Tsai Y-F, Tseng L-M, et al. The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels. PLOS ONE. 2017 Sep 29;12(9):e0185615.
