目的:乳腺肿瘤遗传学在近30年前随着BRCA1和BRCA2基因的发现而出现。分析实践的发展逐渐允许获得测试,其结果现在对女性和男性乳腺癌的管理都有相当大的影响。法国国家妇科和妇产科学院的科学委员会(CNGOF)询问了五名乳房外科专家,肿瘤学和肿瘤遗传学,以制定所用的致癌基因检测标准的摘要,以及检测结果对女性和男性人群的临床意义,有或没有确定的因果变异。在证明遗传风险的情况下,监视,降低风险的策略,并更新了手术和药物治疗(特别是PARP抑制剂)的特异性.
方法:本摘要基于国家和国际遗传风险监测和治疗管理指南,以及最近对过去五年的文献进行的回顾。
结果:尽管技术不断发展,在法国,在暗示有乳腺癌和卵巢癌倾向的情况下,确定因果变异的可能性仍约为10%。在70岁时,具有BRCA1,BRCA2,PALB2,TP53,CDH1和PTEN基因因果变异的女性患乳腺癌的风险估计在35%至85%之间。在这些基因之一中存在因果变异是男性和女性不同建议的主题,关于这两个监视,发病年龄和成像方式根据所涉及的基因而有所不同,和降低风险的手术,一旦风险水平超过30%,女性就有可能出现这种情况,男性仍然例外。在乳腺癌的情况下,PARP抑制剂是BRCA种系突变的有希望的新型治疗方法。
结论:一门学科坚决专注于理解分子机制,筛查和预防医学/外科,肿瘤遗传学目前也涉及新的医疗/外科方法,需要监测其长期利益/风险。
OBJECTIVE: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers. The Sénologie commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant. In the case of proven genetic risk, surveillance, risk-reduction strategies, and the specificities of surgical and medical management (with PARP inhibitors in particular) were updated.
METHODS: This summary was based on national and international guidelines on the monitoring and therapeutic management of genetic risk, and a recent review of the literature covering the last five years.
RESULTS: Despite successive technical developments, the probability of identifying a causal variant in a situation suggestive of a predisposition to breast and ovarian cancer remains around 10% in France. The risk of breast cancer in women with a causal variant of the BRCA1, BRCA2, PALB2, TP53, CDH1 and PTEN genes is estimated at between 35% and 85% at age 70. The presence of a causal variant in one of these genes is the subject of different recommendations for men and women, concerning both surveillance, the age of onset and imaging modalities of which vary according to the genes involved, and risk-reduction surgery, which is possible for women as soon as their risk level exceeds 30% and remains exceptionally indicated for men. In the case of breast cancer, PARP inhibitors are a promising new class of treatment for BRCA germline mutations.
CONCLUSIONS: A discipline resolutely focused on understanding molecular mechanisms, screening and preventive medicine/surgery, oncology genetics is currently also involved in new medical/surgical approaches, the long-term benefits/risks of which will need to be monitored.