Doren A, Vecchiola A, Aguirre B, Villaseca P
a Obstetrics and Gynecology Department, Faculty of Medicine , Universidad Católica del Maule , Talca , Chile.
b Endocrinology Department, Faculty of Medicine , Millenium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile , Santiago , Chile.
Climacteric. 2018 Dec;21(6):529-535. doi: 10.1080/13697137.2018.1514006. Epub 2018 Oct 8.
Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.
编码肿瘤抑制蛋白的BRCA1和BRCA2基因发生突变的女性携带者患乳腺癌和卵巢癌的风险很高。由BRCA致病突变引起的遗传性乳腺癌和卵巢癌发病年龄较早:BRCA1突变的乳腺癌患者诊断时的平均年龄为43岁;50岁时卵巢癌的发病几率高达10%-21%。因此需要在生育期制定预防策略。美国国立综合癌症网络(NCCN)指南规定,BRCA1/2基因检测应从患癌个体开始(BRCA1/2全序列检测);然后,家庭成员应检测是否存在特定的基因突变。已知为携带者的女性需要严格的特定监测策略以实现早期诊断。NCCN建议从25岁开始进行乳腺影像学监测;从30-35岁开始进行卵巢监测。同时,应分析降低风险的策略:手术或药物治疗。在绝经前进行预防性双侧输卵管卵巢切除术时,可能需要雌激素替代疗法。对于BRCA,我们综述了突变携带者的癌症风险、基因检测标准、监测和降低风险策略,以及必要时开具激素治疗的安全性。