Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers
Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers
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DOI：
10.1093/jnci/93.21.1633
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发表时间：
2001-11-07
影响因子：
10.3
通讯作者：
Jenkins, RB
中科院分区：
文献类型：
--
作者：
Hartmann, LC;Sellers, TA;Jenkins, RB
背景：在有乳腺癌家族史的女性中，双侧预防性乳房切除术与继发乳腺癌的风险降低约90%相关。我们研究了BRCA1和BRCA2基因突变的乳腺癌高危女性双侧预防性乳房切除术与乳腺癌风险之间的关系。方法：我们采集了214名高危女性中的176名的血液样本，这些女性参与了我们先前的双侧预防性乳房切除术的回顾性队列研究。我们使用构象敏感凝胶电泳和血液样本的直接序列分析来识别BRCA1和BRCA2突变的女性。从两种不同的外显模型估计了携带者患乳腺癌的概率。结果：我们确定了26名BRCA1或BRCA2基因改变的女性。其中18个突变被认为是有害的，8个突变的临床意义不确定。经过平均13.4年(5.8-28.5年)的随访，26名女性中无一人患上乳腺癌。在214名女性中，已知有3人在预防性乳房切除术后患上乳腺癌。对于其中两名女性，BRCA1和BRCA2筛查结果为阴性，第三名患者没有血液样本。考虑到这名妇女既是突变携带者又是非携带者，对预防性乳房切除术的有效性进行了评估。这些计算预测，突变携带者中应该已经发生了6到9例乳腺癌，这意味着在双侧预防性乳房切除术后，风险降低了89.5%-100%(95%可信区间=41.4%-100%)。结论：预防性乳房切除术不仅与根据乳腺癌家族史被确定为高危女性的继发乳腺癌的发病率显著降低有关，而且与已知的BRCA1或BRCA2突变携带者的乳腺癌发病率也相关。
Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of followup (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculationspredicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5 %-100 % (95 % confidence interval = 41.4 % to 100%). Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.